Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade

ABSTRACT

The invention relates to substituted polycyclic aryl and heteroaryl pyridone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

FIELD OF THE INVENTION

This invention is in the field of anticoagulant therapy, andspecifically relates to compounds, compositions and methods forpreventing and treating thrombotic conditions such as coronary arteryand cerebrovascular disease. More particularly, the invention relates tosubstituted polycyclic aryl and heteroaryl pyridone compounds thatinhibit serine proteases of the coagulation cascade.

BACKGROUND OF THE INVENTION

Physiological systems control the fluidity of blood in mammals [Majerus,P. W. et al: Anticoagulant, Thrombolytic, and Antiplplatelet Drugs. InHardman, J. G. and Limbird, L. E., editors: Goodman & Gilman's ThePharmacological Basis of Therapeutics. 9th edition. New York,McGraw-Hill Book Co., 1996, pp. 1341-1343]. Blood must remain fluidwithin the vascular systems and yet be able to undergo hemostasis,cessation of blood loss from a damaged vessel, quickly. Hemostasis orclotting begins when platelets first adhere to macromolecules insubendothelian regions of an injured and/or damaged vessels. Theseplatelets aggregate to form the primary hemostatic plug and stimulatelocal activation of plasma coagulation factors leading to generation ofa fibrin clot that reinforces the aggregated platelets.

Plasma coagulation factors include factors II, V, VII, VIII, IX, X, XI,and XII; these are also called protease zymogens. These coagulationfactors or protease zymogens are activated by serine proteases leadingto coagulation in a so called “coagulation cascade” or chain reaction[Handin, R. I.: Bleeding and Thrombosis. In Wilson, J., et al. editors:Harrison's Principles of Internal Medicine. 12th Edition, New York,McGraw-Hill Book Co., 1991,p.350]. Coagulation or clotting occurs in twoways through different pathways. An intrinsic or contact pathway leadsfrom XII to XIIa to XIa to IXa and to the conversion of X to Xa. Xa withfactor Va converts prothrombin (II) to thrombin (IIa) leading toconversion of fibrinogen to fibrin. Polymerization of fibrin leads to afibrin clot. An extrinsic pathway is initiated by the conversion ofcoagulation factor VII to VIIa by Xa. The presence of Tissue Factor andVIIa accelerates formation of Xa in the presence of calcium ion andphospholipids. Formation of Xa leads to thrombin, fibrin, and a fibrinclot as described above. The presence of one or more of these manydifferent coagulation factors and two distinct pathways of clottingcould enable the efficacious, selective control and better understandingof parts of the coagulation or clotting process.

While clotting as a result of an injury to a blood vessel is a criticalphysiological process for mammals such as man, clotting can also lead todisease states. A pathological process called thrombosis results whenplatelet aggregation and/or a fibrin clot blocks (i.e., occludes) ablood vessel. Arterial thrombosis may result in ischemic necrosis of thetissue supplied by the artery. When the thrombosis occurs in a coronaryartery, a myocardial infarction or heart attack can result. A thrombosisoccurring in a vein may cause tissues drained by the vein to becomeedematous and inflamed. Thrombosis of a deep vein may be complicated bya pulmonary embolism. Preventing or treating clots in a blood vessel maybe therapeutically useful by inhibiting formation of blood plateletaggregates, inhibiting formation of fibrin, inhibiting thrombusformation, inhibiting embolus formation, and for treating or preventingunstable angina, refractory angina, myocardial infarction, transientischemic attacks, atrial fibrillation, thrombotic stroke, embolicstroke, deep vein thrombosis, disseminated intravascular coagulation,ocular build up of fibrin, and reocclusion or restenosis of recanalizedvessels.

There have been several reports of non-peptidic and peptidic pyridonecompounds that act as an inhibitor of a coagulation factor present inthe coagulation cascade or clotting process. In PCT Patent ApplicationWO 98/47876, Van Boeckel et al. describe peptidic 6-alkylpyridones and2-alkylpyrimidinones as anti-thrombotic compounds. In PCF PatentApplication WO 98/16547, Zhu and Scarborough describe3-(N-heterocyclylamino)4,5,6-substituted-pyridonylacetamides and2,4substituted-5-(N-heterocyclylamino)-pyrimidinonyl-acetamidescontaining amide substituents and having activity against mammalianfactor Xa. In U.S. Pat. No. 5,656,645, Tamura et al. describe4,5,6-substituted-3-aminopyridonyl-acetamides,1,6-substituted-5-aminouracinylacetamides, and2,4-substituted-5-aminopyrimidinonyl-acetamides containing amidesubstituents having a formyl function and having activity againstthrombin. In U.S. Pat. No. 5,658,930, Tamura et al. again describe4,5,6-substituted-3-aminopyridonyl-acetamides,1,6-substituted-5-aminouracinylacetamides, and2,4substituted-5-aminopyrimidinonyl-acetamides containing amidesubstituents having a formyl function and having activity againstthrombin. In PCT Patent Applications 96/18644 and 97/46207, Tamura etal. further describe 4,5,6-substituted-3-aminopyridonylacetamides,1,6-substituted-5-aminouracinyl-acetamides, and2,4substituted-5-amino-pyrimidinonylacetamides containing amidesubstituents having a formyl function and having activity againstthrombin. In PCT Patent Application WO 98/09949, Suzuki et al. describe2-heterocyclylacetamido derivatives of 1,2-diketones and report thatthey inhibit proteases, especially chymase inhibitors. In U.S. Pat. No.5,668,289, Sanderson et al. describe 6-alkyl, 6-cycloalkyl, and6-trifluoromethyl pyridones unsubstituted at the 4 and 5 positions andreported to inhibit thrombin. In PCT Patent Application WO 97/01338,Sanderson et al. describe 6-alkyl, 6-cycloalkyl, and 6-trifluoromethylpyridones unsubstituted at the 4 and 5 positions and reported to inhibitthrombin. In U.S. Pat. No. 5,792,779, Sanderson et al. describesubstituted 4,6-alkyl, 4,6-cycloalkyl, and 4,6-trifluoromethyl pyridoneshaving utility as thrombin inhibitors. In PCT Patent Application WO97/30708, Sanderson et al. describe additional substituted 4,6-alkyl,4,6-cycloalkyl, and 4,6-trifluoromethyl pyridones having utility asthrombin inhibitors. In U.S. Pat. No. 5,869,487, Coburn et al. describepyrido[3,4-B]pyrazines containing a fused 6-methylpyridone functionalityand having utility as thrombin inhibitors. In PCT Patent Application WO98/31670, Sanderson et al. describe additional 4substituted 6-alkyl,6-cycloalkyl, and 6-trifluoromethyl pyridones having utility as thrombininhibitors. In PCT Patent Application WO 98/17274, Coburn et al.disclose substituted 3,4diamino-6-methylpyridones having utility ashuman thrombin inhibitors. In PCT Patent Application WO 98/42342, Isaacset al. describe additional 6-alkyl, cycloalkyl, and trifluoromethylsubstituted pyridones and pyrazinones reported to inhibit humanthrombin.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide compounds that arebeneficial in anticoagulant therapy and that have a general structure:

It is another object of the present invention to provide methods forpreventing and treating thrombotic conditions, such as coronary arterydisease, cerebrovascular disease, and other coagulation relateddisorders. Such thrombotic conditions are prevented and treated byadministering to a patient in need thereof an effective amount ofcompounds of Formula (I).

Various other objects and advantages of the present invention willbecome apparent from the following description of the invention.

DESCRIPTION OF THE INVENTION

The present invention relates to a class of compounds comprisingSubstituted Polycyclic Aryl and Heteroaryl Pyridones, which arebeneficial in anticoagulant therapy for the treatment and prevention ofa variety of thrombotic conditions including coronary artery andcerebrovascular disease, as given in Formula (I):

or a pharmaceutically acceptable salt thereof, wherein;

-   -   J is selected from the group consisting of O and S;    -   J is optionally selected from the group consisting of CH—R⁶ and        N—R⁶ wherein R⁶ is a linear spacer moiety having a chain length        of 1 to 4 atoms linked to the point of bonding of a substituent        selected from the group consisting of R^(4a), R^(4b), R³⁹, R⁴⁰,        R⁵, R¹⁴, and R¹⁵ to form a heterocyclyl ring having 5 through 8        contiguous members;    -   B is formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N with the        proviso that R³², R³³, R³⁴, R³⁵, and R³⁶ are each independently        selected to maintain the tetravalent nature of carbon, trivalent        nature of nitrogen, the divalent nature of sulfur, and the        divalent nature of oxygen;    -   R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵,        and R³⁶ are independently selected from the group consisting of        hydrido, acetarnido, haloacetamido, amidino, guanidino,        dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,        carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino,        acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy,        aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,        perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,        aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl,        halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl,        cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino,        N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,        haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,        haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy,        cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl,        cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl,        halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino,        alkoxyamino, thio, nitro, lower alkylamino, alkylthio,        alkylthioalkyl, arylamino, aralkylamino, arylthio,        arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl,        alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,        heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,        alkylsulfonylalkyl, haloalkylsulfinylalkyl,        haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,        monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl,        monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl,        heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,        heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl,        aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl,        alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky,        alkylenedioxy, haloalkylenedioxy, cycloalkyl,        cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower        cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,        hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino,        hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy,        aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially        saturated heterocyclyl, heteroaryl, heteroaryloxy,        heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl,        heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido,        alkylamidocarbonylamido, arylamidocarbonylamido,        carboalkoxyalkyl, carboalkoxyalkenyl, carboxy, carboaralkoxy,        carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,        phosphono, phosphonoalkyl, diaralkoxyphosphono, and        diaralkoxyphosphonoalkyl;    -   R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independently        optionally Q^(b) with the proviso that no more than one of R¹⁶        and R¹⁹ is Q^(b) at the same time and that Q^(b) is Q^(be);    -   R³² and R³³, R³³ and R³⁴, R³⁴, and R³⁵, and R³⁵ and R³⁶ are        independently optionally selected to form a spacer pair wherein        a spacer pair is taken together to form a linear moiety having        from 3 through 6 contiguous atoms connecting the points of        bonding of said spacer pair members to form a ring selected from        the group consisting of a cycloalkenyl ring having 5 through 8        contiguous members, a partially saturated heterocyclyl ring        having 5 through 8 contiguous members, a heteroaryl ring having        5 through 6 contiguous members, and an aryl with the proviso        that no more than one of the group consisting of spacer pairs        R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵ , and R³⁵ and R³⁶ can be        used at the same time;    -   R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ are        independently optionally selected to form a spacer pair wherein        a spacer pair is taken together to form a linear moiety having        from 3 through 6 contiguous atoms connecting the points of        bonding of said spacer pair members to form a ring selected from        the group consisting of a cycloalkenyl ring having 5 through 8        contiguous members, a partially saturated heterocyclyl ring        having 5 through 8 contiguous members, a heteroaryl ring having        5 through 6 contiguous members, and an aryl with the proviso        that no more than one of the group consisting of spacer pairs R⁹        and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ can be used        at the same time;    -   B is optionally selected from the group consisting of hydrido,        trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl,        C3-C8 alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein        each member of group B is optionally substituted at any carbon        up to and including 6 atoms from the point of attachment of B to        A with one or more of the group consisting of R³², R³³, R³⁴,        R³⁵, and R³⁶;    -   B is optionally selected from the group consisting of C3-C15        cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl,        and C4-C9 partially saturated heterocyclyl, wherein each ring        carbon is optionally substituted with R³³, a ring carbon other        than the ring carbon at the point of attachment of B to A is        optionally substituted with oxo provided that no more than one        ring carbon is substituted by oxo at the same time, ring carbons        and a nitrogen adjacent to the carbon atom at the point of        attachment are optionally substituted with R⁹ or R¹³, a ring        carbon or nitrogen adjacent to the R⁹ position and two atoms        from the point of attachment is optionally substituted with R¹⁰,        a ring carbon or nitrogen adjacent to the R¹³ position and two        atoms from the point of attachment is optionally substituted        with R¹², a ring carbon or nitrogen three atoms from the point        of attachment and adjacent to the R¹⁰ position is optionally        substituted with R¹¹, a ring carbon or nitrogen three atoms from        the point of attachment and adjacent to the R¹² position is        optionally substituted with R³³, and a ring carbon or nitrogen        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   A is selected from the group consisting of single covalent bond,        (W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr        is an integer selected from 0 through 1, pa is an integer        selected from 0 through 6, and W⁷ is selected from the group        consisting of O, S, C(O), C(S), C(O)S, C(S)O, C(O)N(R⁷),        C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),        (R⁷)NS(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), C(NR⁷)N(R⁷)        (R⁷)NC(NR⁷) (R⁷)NC(NR⁷)NR⁷, and N(R⁷) with the proviso that no        more than one of the group consisting of rr and pa can be 0 at        the same time;    -   R⁷ and R⁸ are independently selected from the group consisting        of hydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and        alkoxyalkyl;    -   R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the group        consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl,        alkoxy, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl,        cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl,        haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,        halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,        carboxy, carboxyalkyl, carboalkoxy, carboxamide, and        carboxamidoalkyl;    -   R¹⁴ and R³⁸ can be independently selected from the group        consisting of acyl, aroyl, and heteroaroyl with the proviso that        acyl is selected from other than formyl and 2-oxoacyl;    -   Ψ is selected from the group consisting of NR⁵, O, C(O), C(S),        S, S(O), S(O)₂, ON(R⁵), P(O)(R⁸), and CR³⁹R⁴⁰;    -   R⁵ is selected from the group consisting of hydrido, hydroxy,        amino, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, and        heteroaroyl;    -   R³⁹ and R⁴⁰ are independently selected from the group consisting        of hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl,        heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl,        haloalkoxy, haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl,        carboxy, carboxyalkyl, carboalkoxy, carboxamide, and        carboxamidoalkyl;    -   R¹, R² and X⁰ are independently selected from the group        consisting of Z⁰-Q, hydrido, alkyl, alkenyl, and halo;    -   R¹ and X⁰ are independently optionally selected from the group        consisting of amino, aminoalkyl, alkylamino, amidino, guanidino,        hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol,        alkylthio, dialkylsulfonium, trialkylphosphonium,        dialkylsulfoniumalkyl, heteroarylamino, nitro, arylamino,        aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,        aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl,        cyano, and phosphono;    -   X⁰ and R¹ and R¹ and R², with the proviso that no more than one        of the group consisting of spacer pair X⁰ and R¹ and spacer pair        R¹ and R² is be used at the same time, are optionally selected        to be —W═X—Y=Z- wherein —W═X—Y=Z- forms a ring selected from the        group consisting of a heteroaryl ring having from 5 through 6        contiguous members and an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹), C(R¹²), N, N(R¹⁰), O, S and        a covalent bond with the provisos that W, X, Y, and Z can be        independently selected to be a covalent bond when one of W, X,        Y, and Z is selected from the group consisting of N, N(R¹⁰), O,        and S, no more than one of W, X, Y, and Z can be selected from        the group consisting of O and S, and no more than three. of W,        X, Y, and Z can be selected from the group consisting of N and        N(R¹⁰);    -   X⁰ and R¹ and R¹ and R² spacer pairs are independently        optionally selected to be taken together to form a spacer pair        wherein the spacer pair forms a linear moiety having from 3        through 6 contiguous atoms connecting the points of bonding of        said spacer pair members to form a ring selected from the group        consisting of a cycloalkenyl ring having from 5 through 8        contiguous members and a partially saturated heterocyclyl ring        having from 5 through 8 contiguous members, wherein said spacer        pair is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³ and with the proviso        that no more than one of the group consisting of spacer pair X⁰        and R¹ and spacer pair R¹ and R² is present at the same time;    -   Z⁰ is selected from the group consisting of covalent single        bond, (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1        through 6, (CH(R⁴¹)_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are        integers independently selected from 0 through 3 and W⁰ is        selected from the group consisting of O, S, C(O), C(S), C(O)O,        C(S)O, C(O)S, C(S)S, C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹),        (R⁴¹)NC(S), OC(O)N(R⁴¹), (R⁴¹)NC(O)O, SC(S)N(R⁴¹), (R⁴¹)NC(S)S,        SC(O)N(R⁴¹), (R⁴¹)NC(O)S, OC(S)N(R⁴¹), (R⁴¹)NC(S)O,        N(R⁴²)C(O)N(R⁴¹) (R⁴¹)NC(O)N(R⁴²), N(R⁴²)C(S)N(R⁴¹),        (R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹), N(R⁴¹)S(O)₂, Se,        Se(O), Se(O)₂, Se(O)₂N(R⁴¹), N(R⁴¹)Se(O)₂, P(O)(R⁸),        N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁴¹), ON(R⁴¹), and SiR²⁸R²⁹, and        (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integers        independently selected from 0 through 2 and W²²is selected from        the group consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene),        ethynylidene (C≡C; 1,2-ethynyl), 1,2-cyclopropyl,        1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,        1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,        3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,        2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,        3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,        2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the        provisos that R⁴¹ and R⁴² are selected from other than halo and        cyano when directly bonded to N and Z⁰ is directly bonded to the        pyridone ring;    -   R⁴¹ and R⁴² are independently selected from the group consisting        of amidino, hydroxyamino, hydrido, hydroxy, amino, halo, cyano,        aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl,        heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl,        aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl,        cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,        cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,        halocycloalkenyl, haloalkoxy, haloalkoxyalkyl,        haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl,        halocycloalkenyloxyalkyl, saturated heterocyclyl, partially        saturated heterocyclyl, heteroaryl, heteroaralkyl,        heteroarylthioalkyl, heteroaralkylthioalkyl, alkylsulfonyl,        haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl,        aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl,        heteroarylsulfonylalkyl, heteroarylsulfonyl, and        aralkylsulfonylalkyl;    -   Q is formula (II):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N, with the        proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently        selected to maintain the tetravalent nature of carbon, trivalent        nature of nitrogen, the divalent nature of sulfur, and the        divalent nature of oxygen;    -   Q is optionally selected from formula (III):        wherein D³, D⁴, J⁵, and J⁴ are independently selected from the        group consisting of C, N, O, and S, no more than one of D³, D⁴,        J³, and J⁴ is O, no more than one of D³, D⁴, J³ and J⁴ is S, and        no more than three of D¹, D², J¹, and J² are N with the proviso        that R⁹, R¹⁰, R¹¹, and R¹² are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   Q is optionally selected from the group consisting of hydrido,        alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl,        alkynyl, saturated heterocyclyl, partially saturated        heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl,        cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl,        cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl,        halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,        haloalkenyloxyalkyl, halocycloalkoxyalkyl, and        halocycloalkenyloxyalkyl with the proviso that Z⁰ is selected        from other than a single covalent bond when Q is hydrido;    -   K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1        through 2;    -   R^(4a) and R^(4b) are independently selected from the group        consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl,        alkyl, alkenyl, alkoxyalkyl, aralkyl, heteroaralkyl,        alkylthioalkyl, haloalkyl, haloalkenyl, and cyanoalkyl;    -   E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selected        from the group consisting of a covalent single bond, O, S, C(O),        C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O),        C(S)N(R⁷), (R⁷)NC(S), OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷),        (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O,        N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸),        S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),        C(O)N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷),        ON(R⁷), CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and        C═CR^(4a)R^(4b);    -   K is optionally (CH(R¹⁴))_(j)-T wherein j is selected from a        integer from 0 through 2 and T is selected from the group        consisting of single covalent bond, O, S, and N(R⁷) with the        proviso that (CH(R¹⁴))_(j) is bonded to the pyridone ring;    -   E⁰ is optionally E², when K is (CH(R¹⁴))_(j)-T, wherein E² is        selected from the group consisting of a covalent single bond,        C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O),        C(S)N(R⁷), (R⁷)NC(S), (R⁷)NC(O)O, (R⁷)NC(S)S, (R⁷)NC(O)S,        (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),        (R⁷)NC(S)N(R⁸) S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂,        S(O)₂N(H)C(O), C(O)N(H)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),        P(O)(R⁸)N(R⁷), and N(R⁷);    -   K is optionally G-(CH(R¹⁵))_(k) wherein k is selected from an        integer from 1 through 2 and G is selected from the group        consisting of O, S, and N(R⁷) with the proviso that R¹⁵ is other        than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and        sulfhydryl when k is 1;    -   E⁰ is optionally E³ when K is G-(CH(R¹⁵))_(k), wherein E³ is        selected from the group consisting of a covalent single bond, O,        S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O),        C(S)N(R⁷), (R⁷)NC(S), OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷),        (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O,        N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸),        S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),        P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), CR^(4a)═CR^(4b), ethynylidene        (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is        independently selected from the group consisting of C and N⁺ no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, no        more than three of D⁵, D⁶, J⁵, and J⁶ is N when K² is N⁺, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N when K² is carbon        with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each        independently selected to maintain the tetravalent nature of        carbon, trivalent nature of nitrogen, the divalent nature of        sulfur, and the divalent nature of oxygen;    -   R¹⁶ and R¹⁷ are optionally independently taken together to form        a linear moiety spacer having from 3 through 6 contiguous atoms        connected to form a ring selected from the group consisting of a        cycloalkenyl ring having from 5 through 8 contiguous members, a        partially saturated heterocyclyl ring having from 5 through 8        contiguous members, a heteroaryl having from 5 through 6        contiguous members, and an aryl;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, ³⁰        NR²⁰R²¹R²², oxy, alkyl, aminoalkylenyl, alkylamino,        dialkylamino, dialkylsulfoniumalkyl, acylamino and Q^(be),        wherein Q^(be) is hydrido and R²⁰, R²¹, and R²² are        independently selected from the group consisting of hydrido,        amino, alkyl, hydroxy, alkoxy, aminoalkylenylalkylamino,        dialkylamino, and hydroxyalkyl with the provisos that no more        than one of R²⁰, R²¹, and R²² is hydroxy, alkoxy, alkylamino,        amino, and dialkylamino at the same time and that R²⁰, R²¹, and        R²² must be other than be hydroxy, alkoxy, alkylamino, amino,        and dialkylamino when K² is N⁺;    -   R²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² are independently        optionally selected to form a spacer pair wherein a spacer pair        is taken together to form a linear moiety having from 4 through        7 contiguous atoms connecting the points of bonding of said        spacer pair members to form a heterocyclyl ring having 5 through        8 contiguous members with the proviso that no more than one of        the group consisting of spacer pairs R²⁰ and R²¹, R²⁰ and R²²,        and R²¹ and R²² is used at the same time;    -   Q^(b) is optionally selected from the group consisting of        N(R²⁶)SO₂N(R²³)(R²⁴), N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵,        N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵ with the proviso that no more        than one of R²³, R²⁴, and R²⁶ is hydroxy, alkoxy, alkylamino,        amino, and dialkylamino when two of the group consisting of R²³,        R²⁴, and R²⁶ are bonded to the same atom;    -   Q^(b) is optionally selected from the group consisting of        dialkylsulfonium, trialkylphosphonium, C(NR²⁵)NR²³R²⁴,        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)C(O)N(R²³)(R²⁴),        N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵, C(O)N(R²⁶)C(NR²⁵)N(R²⁵)(R²³),        C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),        ON(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),        C(NR²⁵)SR⁵, C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with the provisos that        no more than one of R²³, R²⁴, and R²⁶ can be hydroxy, alkoxy,        alkylaminol, amino, or dialkylamino when two of the group        consisting of R²³, R²⁴, and R²⁶ are bonded to the same atom and        that said Q^(b) group is bonded directly to a carbon atom;    -   R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the group        consisting of hydrido, alkyl, hydroxy, alkoxy, aminoalkylenyl,        alkylamino, dialkylamino, amino, and hydroxyalkyl;    -   R²³ and R²⁴ are optionally taken together to form a linear        spacer moiety having from 4 through 7 contiguous atoms        connecting the points of bonding to form a heterocyclyl ring        having 5 through 8 contiguous members;    -   Q is selected from the group consisting of a single covalent        bond, (CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected        from 0 through 1, b is an integer selected from 1 through 4, and        W⁰ is selected from the group consisting of O, S, C(O), C(S),        C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴),        (R¹⁴)NC(S), OC(O)N(R¹⁴), SC(S)N(R¹⁴), SC(O)N(R¹⁴), OC(S)N(R¹⁴),        N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),        (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂,        P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴),        (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integers        independently selected from 1 through 4, and W¹ is selected from        the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,        C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S),        OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴),        (R¹⁴)NC(O)S, OC(S)N(R ¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴),        (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O),        S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),        P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and        (CH(R¹⁴))_(e)—W²²—(CH(R¹⁵))_(h) wherein e and h are integers        independently selected from 0 through 2 and W²² is selected from        the group consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene),        ethynylidene (C≡C; 1,2-ethynyl), 1,2-cyclopropyl,        1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,        1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,        3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,        2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,        3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,        2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the        provisos that R¹⁴ and R¹⁵ are selected from other than halo and        cyano when directly bonded to N and that (CR³⁷R³⁸)_(b),        (CH(R¹⁴))_(c), (CH(R¹⁴))_(e) and are bonded to E;    -   Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is selected from        the group consisting of (CR³⁷R³⁸)_(f) wherein f is an integer        selected from 1 through 6, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d)        wherein c and d are integers independently selected from 1        through 4, and W¹ is selected from the group consisting of W¹ is        selected from the group consisting of O, S, C(O), C(S), C(O)O,        C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴),        (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S,        SC(O)N(R¹⁴), (R¹⁴)NC(O)S, OC(S)N(R¹⁴) (R¹⁴)NC(S)O,        N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),        (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂,        P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and        (CH(R ))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h are integers        independently selected from 0 through 2 and W² is selected from        the group consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C;        1,2-ethynyl), and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and        R¹⁵ are selected from other than halo and cyano when directly        bonded to N and that (CR³⁷ R³⁸)_(f), (CH(R¹⁴))_(c), and        (CH(R¹⁴))_(e) are bonded to E⁰;    -   Y⁰ is optionally Q^(b)-Q^(sss) wherein Q^(sss) is        (CH(R³⁸))_(r)—W³, r is an integer selected from 1 through 3, W³        is selected from the group consisting of 1,1-cyclopropyl,        1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl,        1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,        3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,        1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,        2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,        3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl,        1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,        2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,        2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,        4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,        4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl,        2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,        3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,        2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,        2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and        3,5-tetrahydropyranyl, and each carbon and hyrido containing        nitrogen member of the ring of the W³ other than the points of        attachment is optionally substituted with one or more of the        group consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that        (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest        numbered substituent position of each W³;

Y⁰ is optionally Q^(b)-Q^(sssr) wherein Q^(sssr) is (CH(R³⁸))_(r)—W⁴, ris an integer selected from 1 through 3, W⁴ is selected from the groupconsisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl, and each carbon andhydrido containing nitrogen member of the ring of the W⁴ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the provisos that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to highest numbersubstituent position of each W⁴;

-   -   Y⁰ is optionally Q^(b)-Q^(ssss) wherein Q^(ssss) is        (CH(R³⁸))_(r)—W⁵, r is an integer selected from 1 through 3, W⁵        is selected from the group consisting of 1,4-indenyl,        1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,        2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,        3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,        2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,        3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,        2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,        2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,        3,6-benzothiophenyl, 3,7-benzothiophenyl,        2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,        3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,        3,7-imidazo( 1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl,        2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,        3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,        2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,        1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,        3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,        2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,        3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,        1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,        1,8-naphthyl, 2,4naphthyl, 2,5-naphthyl, 2,6-naphthyl,        2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,        2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,        3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,        4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,        1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,        1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,        3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,        3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,        4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,        3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,        4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and        4,8-cinnolinyl, and each carbon and hydrido containing nitrogen        member of the ring of the W other than the points of attachment        is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)        is bonded to lowest number substituent position of each W⁵ and        that (CH(R³⁸))_(r) is bonded to E⁰;    -   Y⁰ is optionally Q^(b)-Q^(ssssr) wherein Q^(sssr) is        (CH(R³⁸))_(r)—W⁶, r is an integer selected from 1 through 3, W⁶        is selected from the group consisting of 1,4-indenyl,        1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,        2,5-indenyl, 2,4-indenyl, 3,4indenyl, 3,5-indenyl, 3,6-indenyl,        3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,        2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,        3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,        2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,        2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,        3,6-benzothiophenyl, 3,7-benzothiophenyl,        2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,        3,5-imidazo( 1,2-a)pyridinyl, 3,6-imidazo( 1,2-a)pyridinyl,        3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl,        2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,        3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,        2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,        1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,        3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,        2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,        3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,        1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,        1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,        2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,        2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,        3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,        4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,        1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,        1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,        3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,        3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,        4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,        3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,        4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and        4,8-cinnolinyl, and each carbon and hydrido containing nitrogen        member of the ring of the W⁶ other than the points of attachment        is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)        is bonded to highest number substituent position of each W⁶ and        that (CH(R³⁸))_(r) is bonded to E⁰.

In another embodiment of compounds of Formula I or a pharmaceuticallyacceptable salt thereof,

-   -   J is selected from the group consisting of O and S;    -   B is formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N;    -   R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵,        and R³⁶ are independently selected from the group consisting of        hydrido, acetamido, haloacetamido, amidino, guanidino,        dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,        carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino,        acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy,        aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,        perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,        aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl,        halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl,        cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino,        N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,        haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,        haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy,        cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl,        cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl,        halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino,        alkoxyamino, thio, nitro, lower alkylamino, alkylthio,        alkylthioalkyl, arylamino, aralkylamino, arylthio,        arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl,        alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,        heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,        alkylsulfonylalkyl, haloalkylsulfinylalkyl,        haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,        monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl,        monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl,        heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,        heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl,        aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl,        alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky,        alkylenedioxy, haloalkylenedioxy, cycloalkyl,        cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower        cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,        hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino,        hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy,        aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially        saturated heterocyclyl, heteroaryl, heteroaryloxy,        heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl,        heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido,        alkylamidocarbonylamido, arylamidocarbonylamido,        carboalkoxyalkyl, carboalkoxyalkenyl, carboxy, carboaralkoxy,        carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,        phosphono, phosphonoalkyl, diaralkoxyphosphono, and        diaralkoxyphosphonoalkyl;    -   R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independently        optionally Q^(b) with the proviso that no more than one of R¹⁶        and R¹⁹ is Q^(b) at the same time and that Q^(b) is Q^(be);    -   B is optionally selected from the group consisting of hydrido,        trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl,        C3-C8 alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein        each member of group B is optionally substituted at any carbon        up to and including 6 atoms from the point of attachment of B to        A with one or more of the group consisting of R³², R³³, R³⁴,        R³⁵, and R³⁶;

B is optionally selected from the group consisting of C3-C12 cycloalkyl,C5-C10 cycloalkenyl, and C4-C9 saturated heterocyclyl, wherein each ringcarbon is optionally substituted with R³³, a ring carbon other than thering carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and nitrogen adjacentto the carbon atom at the point of attachment are optionally substitutedwith R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹ positionand two atoms from the point of attachment is optionally substitutedwith R¹⁰, a ring carbon or nitrogen adjacent to the R¹³ position and twoatoms from the point of attachment is optionally substituted with R¹², aring carbon or nitrogen three atoms from the point of attachment andadjacent to the R¹⁰ position is optionally substituted with R¹¹, a ringcarbon or nitrogen three atoms from the point of attachment and adjacentto the R¹² position is optionally substituted with R³³, and a ringcarbon or nitrogen four atoms from the point of attachment and adjacentto the R¹¹ and R³³ positions is optionally substituted with R³⁴;

-   -   A is selected from the group consisting of single covalent bond,        (W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr        is an integer selected from 0 through 1, pa is an integer        selected from 0 through 6, and W⁷ is selected from the group        consisting of O, S, C(O), C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O),        (R⁷)NC(S), and N(R⁷) with the proviso that no more than one of        the group consisting of rr and pa can be 0 at the same time;    -   R⁷ and R⁸ are independently selected from the group consisting        of hydrido, hydroxy, alkyl, and alkoxyalkyl;    -   R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the group        consisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl,        haloalkyl, haloalkoxy, and haloalkoxyalkyl;    -   R¹⁴ and R³⁸ can be independently selected from the group        consisting of aroyl and heteroaroyl;    -   Ψ is selected from the group consisting of NR⁵, C(O), and S(O)₂;    -   R⁵ is selected from the group consisting of hydrido, hydroxy,        alkyl, and alkoxy;    -   R³⁹ and R⁴⁰ are independently selected from the group consisting        of hydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl,        haloalkyl, haloalkoxy, and haloalkoxyalkyl;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy,        haloalkylthio, amino, aminoalkyl, alkylamino, amidino,        guanidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,        alkoxyamino, thiol, alkylthio, and phosphono;    -   X⁰ and R¹ and R¹ and R², with the proviso that no more than one        of the group consisting of spacer pair X⁰ and R¹ and spacer pair        R¹ and R² is be used at the same time, are optionally selected        to be —W═X—Y=Z- wherein —W═X—Y=Z- forms a ring selected from the        group consisting of a heteroaryl ring having from 5 through 6        contiguous members and an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹), C(R¹²), N, N(R¹⁰), O, S and        a covalent bond with the provisos that W, X, Y, and Z can be        independently selected to be a covalent bond when one of W, X,        Y, and Z is selected from the group consisting of N, N(R¹⁰), O,        and S, no more than one of W, X, Y, and Z can be selected from        the group consisting of O and S, and no more than three of W, X,        Y, and Z can be selected from the group consisting of N and        N(R¹⁰);    -   X⁰ and R¹ and R¹ and R² spacer pairs are independently        optionally selected to be taken together to form a spacer pair        wherein the spacer pair forms a linear moiety having from 3        through 6 contiguous atoms connecting the points of bonding of        said spacer pair members to form a ring selected from the group        consisting of a cycloalkenyl ring having from 5 through 8        contiguous members and a partially saturated heterocyclyl ring        having from 5 through 8 contiguous members, wherein said spacer        pair is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³ and with the proviso        that no more than one of the group consisting of spacer pair X⁰        and R¹ and spacer pair R¹ and R² is present at the same time; R²        is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1        through 3, (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are        integers independently selected from 0 through 3 and W⁰ is        selected from the group consisting of O, S, C(O), S(O), S(O)₂,        N(R⁴¹), and ON(R⁴¹), and (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein        e and h are integers independently selected from 0 through 2 and        W²² is selected from the group consisting of CR⁴¹═CR⁴²,        1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,        1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,        2,4morpholinyl, 2,6-morpholinyl, 3,4morpholinyl,        3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,        2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,        1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,        2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,        1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,        2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl,        2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and        3,4-tetrahydrofuranyl, with the proviso that Z⁰ is directly        bonded to the pyridone ring;    -   R⁴¹ and R⁴² are independently selected from the group consisting        of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;    -   Q is selected from the group consisting of hydrido, with the        proviso that Z⁰ is other than a covalent single bond, the        formula (II):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ is N, with the        proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently        selected to maintain the tetravalent nature of carbon, trivalent        nature of nitrogen, the divalent nature of sulfur, and the        divalent nature of oxygen;    -   K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1        through 2;    -   R^(4a) and R^(4b) are independently selected from the group        consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,        alkylthioalkyl, and haloalkyl;    -   E⁰ is selected from the group consisting of a covalent single        bond, C(O), C(S), C(O)N(R⁷), (R⁷)NC(O), S(O)₂, (R⁷)NS(O)₂, and        S(O)₂N(R⁷);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N when K² is carbon        with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each        independently selected to maintain the tetravalent nature of        carbon, trivalent nature of nitrogen, the divalent nature of        sulfur, and the divalent nature of oxygen;    -   Q is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,        aminoalkylenyl, and Q^(be), wherein Q^(be) is hydrido and R²⁰,        R²¹, and R²² are independently selected from the group        consisting of hydrido, alkyl, hydroxy, amino, aminoalkylenyl,        dialkylamino, alkylamino, and hydroxyalkyl with the proviso that        no more than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino,        or dialkylamino at the same time;    -   Q^(b) is optionally selected from the group consisting of        C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),        C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),        and ON(R²⁶)C(NR²⁵)N(R²³)(R²⁴) with the provisos that no more        than one of R²³, R²⁴, and R²⁶ is hydroxy, alkylamino, amino, or        dialkylamino when two of the group consisting of R²³, R²⁴, and        R²⁶ are bonded to the same atom;    -   R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the group        consisting of hydrido, alkyl, hydroxy, amino, alkylenylamino,        dialkylamino, alkylamino, and hydroxyalkyl;    -   Q^(s) is selected from the group consisting of a single covalent        bond, (CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected        from 0 through 1, b is an integer selected from 1 through 5, and        WO is selected from the group consisting of O, C(O), S(O),        S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴),        (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integers        independently selected from 1 through 4 and W¹ is selected from        the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,        C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S),        OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴),        (R¹⁴)NC(O)S, OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴),        (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O),        S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),        P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and        (CH(R¹⁴))_(e)—W²²—(CH(R¹⁵))_(h) wherein e and h are integers        independently selected from 0 through 2 and W²² is selected from        the group consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene),        ethynylidene (C≡C; 1,2-ethynyl), 1,2-cyclopropyl,        1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,        1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,        3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,        2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,        3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,        2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the        provisos that R¹⁴ and R¹⁵ are selected from other than halo and        cyano when directly bonded to N and that (CR³⁷R³⁸)_(b),        (CH(R¹⁴))_(c), and (CH(R¹⁴))_(e) are bonded to E⁰;    -   Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is selected from        the group consisting of (CR³⁷R³⁸)_(f) wherein f is an integer        selected from 1 through 4, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d)        wherein c and d are integers independently selected from 1        through 2, and W¹ is selected from the group consisting of W¹ is        selected from the group consisting of O, S, C(O), C(O)N(R¹⁴),        (R¹⁴)NC(O), N(R⁵⁴)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁴), ON(R¹⁴),        and (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h are integers        independently selected from 0 through 2 and W² is selected from        the group consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C;        1,2-ethynyl), and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and        R¹⁵ are selected from other than halo when directly bonded to N        and that (CR³⁷R )_(f), (CH(R¹⁴))_(c), and (CH(R¹⁴))_(e) are        bonded to E⁰;    -   Y⁰ is optionally Q^(b)-Q^(sss) wherein Q^(sss) is        (CH(R³⁸))_(r)—W³, r is an integer selected from 1 through 2, W³        is selected from the group consisting of 1,1-cyclopropyl,        1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl,        1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,        3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,        1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,        2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,        3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl,        1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,        2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,        2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,        4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,        4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl,        2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,        3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,        2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,        2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and        3,5-tetrahydropyranyl, and each carbon and hyrido containing        nitrogen member of the ring of the W³ other than the points of        attachment is optionally substituted with one or more of the        group consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that        (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest        numbered substituent position of each W³;    -   Y⁰ is optionally Q^(b)-Q^(sssr) wherein Q^(sssr) is        (CH(R³⁸))_(r)—W⁴, r is an integer selected from 1 through 2, W⁴        is selected from the group consisting of 1,2-cyclobutyl,        1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,        3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,        1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,        2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,        3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl,        1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,        2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,        2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,        4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,        4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl,        2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,        3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,        2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,        2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and        3,5-tetrahydropyranyl, and each carbon and hyrido containing        nitrogen member of the ring of the W⁴ other than the points of        attachment is optionally substituted with one or more of the        group consisting of R⁹, R¹⁰, R¹¹, and R¹², with the provisos        that (CH(R³⁸))_(r)—W⁵, is bonded to E⁰ and Q^(b) is bonded to        highest number substituent position of each W⁴;    -   Y⁰ is optionally Q^(b)-Q^(ssss) wherein Q^(ssss) is        (CH(R³⁸))_(r)—W⁵, r is an integer selected from 1 through 2, W⁵        is selected from the group consisting of 1,4-indenyl,        1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,        2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,        3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,        2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,        3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,        2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,        2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,        3,6-benzothiophenyl, 3,7-benzothiophenyl,        2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,        3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,        3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl,        2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,        3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,        2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,        1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,        3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,        2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,        3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,        1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,        1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,        2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,        2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,        3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,        4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,        1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,        1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,        3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,        3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,        4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,        3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,        4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and        4,8-cinnolinyl, and each carbon and hyrido containing nitrogen        member of the ring of the W⁵ other than the points of attachment        is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)        is bonded to lowest number substituent position of each W⁵ and        that (CH(R³⁸))_(r) is bonded to E⁰;    -   Y⁰ is optionally Q^(b)-Q^(ssssr) wherein Q^(ssssr) is        (CH(³⁸))_(r)—W⁶, r is integer selected from 1 through 2, W⁶ is        selected from the group consisting of 1,4-indenyl, 1,5-indenyl,        1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,        2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,        2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl,        2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl,        3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl,        2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl,        3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl,        3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,        3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo( 1,2-a)pyridinyl,        3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl,        2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl,        3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl,        1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl,        2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl,        3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl,        2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,        3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,        3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,        1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,        2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,        2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,        3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,        3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,        4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,        1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,        3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,        3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,        4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl,        3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,        3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl,        and 4,8-cinnolinyl, and each carbon and hyrido containing        nitrogen member of the ring of the W⁶ other than the points of        attachment is optionally substituted with one or more of the        group consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that        Q^(b) is bonded to highest number substituent position of each        W⁶ and that (CH(R³⁸))_(r) is bonded to E⁰.

In a preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula:    -   R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵, and R³⁶ are        independently selected from the group consisting of hydrido,        acetamido, haloacetamido, amidino, guanidino, alkylenedioxy,        haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,        haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, lower        alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl,        alkylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl,        cycloalkylalkyl, alkylsulfonamido, alkylaminosulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,        alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl,        haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl,        aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy,        carboxamido, carboxamidoalkyl, and cyano;    -   R⁹, R¹⁰, R¹¹, R¹², and R¹³ are optionally selected from the        group consisting of heteroaryl and heterocyclyl with the proviso        that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are substitutents for other than        B;    -   R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independently        optionally Q^(b) with the proviso that no more than one of R¹⁶        and R¹⁹ is Q^(b) at the same time and that Q^(b) is Q^(be);    -   B is optionally, with the proviso that R¹ and R² are selected        from the group consisting of a spacer pair and —W═X—Y=Z-,        Formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N;    -   B is optionally selected from the group consisting of hydrido,        trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl,        C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group        B is optionally substituted at any carbon up to and including 6        atoms from the point of attachment of B to A with one or more of        the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;    -   B is selected from the group consisting of C3-C12 cycloalkyl and        C4 heterocyclyl, wherein each ring carbon is optionally        substituted with R³³, a ring carbon other than the ring carbon        at the point of attachment of B to A is optionally substituted        with oxo provided that no more than one ring carbon is        substituted by oxo at the same time, ring carbons and a nitrogen        adjacent to the carbon at the point of attachment are optionally        substituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent        to the R⁹ position and two atoms from the point of attachment is        optionally substituted with R¹⁰, a ring carbon or nitrogen        adjacent to the R¹³ position and two atoms from the point of        attachment is optionally substituted with R¹², a ring carbon or        nitrogen three atoms from the point of attachment and adjacent        to the R¹⁰ position is optionally substituted with R¹¹, a ring        carbon or nitrogen three atoms from the point of attachment and        adjacent to the R¹² position is optionally substituted with R³³,        and a ring carbon or nitrogen four atoms from the point of        attachment and adjacent to the R¹¹ and R²³ positions is        optionally substituted with R³⁴;    -   B is optionally, with the proviso that R¹ and R² are selected        from the group consisting of a spacer pair and —W═X—Y=Z-, a        C5-C9 saturated heterocyclyl, wherein each ring carbon is        optionally substituted with R³³, a ring carbon other than the        ring carbon at the point of attachment of B to A is optionally        substituted with oxo provided that no more than one ring carbon        is substituted by oxo at the same time, ring carbons and        nitrogen adjacent to the carbon atom at the point of attachment        are optionally substituted with R⁹ or R¹³, a ring carbon or        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, a ring        carbon or nitrogen adjacent to the R¹³ position and two atoms        from the point of attachment is optionally substituted with R¹²,        a ring carbon or nitrogen three atoms from the point of        attachment and adjacent to the R¹⁰ position is optionally        substituted with R¹¹, a ring carbon or nitrogen three atoms from        the point of attachment and adjacent to the R¹² position is        optionally substituted with R³³, and a ring carbon or nitrogen        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   A is selected from the group consisting of single covalent bond,        (W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr        is an integer selected from 0 through 1, pa is an integer        selected from 0 through 6, and W⁷ is selected from the group        consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷) with        the proviso that no more than one of the group consisting of rr        and pa is 0 at the same time;    -   R⁷ is selected from the group consisting of hydrido, hydroxy,        and alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, hydroxy,        halo, alkyl, and haloalkyl;    -   Ψ is selected from the group consisting of NH and NOH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy,        haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy,        hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and        alkylthio;    -   X⁰ and R¹ and R¹ and R², with the proviso that no more than one        of the group consisting of spacer pair X⁰ and R¹ and spacer pair        R¹ and R² is be used at the same time, are optionally selected        to be —W═X—Y=Z- wherein —W═X—Y=Z- forms a ring selected from the        group consisting of a heteroaryl ring having from 5 through 6        contiguous members and an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹) C(R¹²), N, N(R¹⁰), O, S and        a covalent bond with the provisos that W, X, Y, and Z can be        independently selected to be a covalent bond when one of W, X,        Y, and Z is selected from the group consisting of N, N(R¹⁰), O,        and S, no more than one of W, X, Y, and Z can be selected from        the group consisting of O and S, and no more than three of W, X,        Y, and Z can be selected from the group consisting of N and        N(R¹⁰);    -   X⁰ and R¹ and R¹ and R² spacer pairs are independently        optionally selected to be taken together to form a spacer pair        wherein the spacer pair forms a linear moiety having from 3        through 6 contiguous atoms connecting the points of bonding of        said spacer pair members to form a ring selected from the group        consisting of a cycloalkenyl ring having from 5 through 8        contiguous members and a partially saturated heterocyclyl ring        having from 5 through 8 contiguous members, wherein said spacer        pair is optionally substituted with one or more of the group        consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³ and with the proviso        that no more than one of the group consisting of spacer pair X⁰        and R¹ and spacer pair R¹ and R² -is present at the same time;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1        through 3, (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are        integers independently selected from 0 through 3 and W⁰ is        selected from the group consisting of O, S, C(O), S(O), N(R⁴¹),        and ON(R⁴¹), and (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h        are integers independently selected from 0 through 1 and W²² is        selected from the group consisting of CR⁴¹═CR⁴²,        1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,        1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,        2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,        3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,        2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,        1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,        2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,        1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,        2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl,        2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and        3,4-tetrahydrofuranyl, with the proviso that Z⁰ -is directly        bonded to the pyridone ring;    -   R⁴¹ and R⁴² are independently selected from the group consisting        of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;    -   Q is selected from the group consisting of hydrido, with the        proviso that Z⁰ is other than a covalent single bond, and the        formula (II):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N, with the        proviso that R⁹,R¹⁰, R¹¹, R¹², and R¹³ are each independently        selected to maintain the tetravalent nature of carbon, trivalent        nature of nitrogen, the divalent nature of sulfur, and the        divalent nature of oxygen;    -   K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1        through 2;    -   R^(4a) and R^(4b) are independently selected from the group        consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,        alkylthioalkyl, and haloalkyl;    -   E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selected        from the group consisting of a covalent single bond, C(O), C(S),        C(O)N(R⁷), (R⁷)NC(O), S(O)₂, (R⁷)NS(O)₂, and S(O)₂N(R⁷);    -   Y is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N with the proviso that        R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino, lower        alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,        haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, alkylenylamino, haloalkoxyalkyl, carboalkoxy, and        cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹,        aminoalkylenyl, Q^(be) wherein Q^(be) is hydrido,        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisos        that no more than one of R²⁰ and R²¹ is hydroxy, amino,        alkylamino, or dialkylamino at the same time and that no more        than one of R²³ and R²⁴ is hydroxy, amino, alkylamino, or        dialkylamino at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, alkyl, hydroxy, aminoalkylenyl,        amino, dialkylamino, alkylamino, and hydroxyalkyl;    -   Q^(s) is selected from the group consisting of a single covalent        bond, (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1        through 4, and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d        are integers independently selected from 1 through 3 and W¹ is        selected from the group consisting of C(O)N(R¹⁴), (R¹⁴)NC(O),        S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the        provisos that R¹⁴ is selected from other than halo when directly        bonded to N and that (CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) are bonded        to E⁰;    -   R¹⁴ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   R³⁷ and R³⁸ are independently selected from the group consisting        of hydrido, alkyl, and haloalkyl;    -   R³⁸ is optionally selected from the group consisting of aroyl        and heteroaroyl;    -   Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is        (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are integers        independently selected from 1 through 2 and W² is        CR^(4a)═CR^(4b) with the proviso that (CH(R¹⁴))_(e) is bonded to        E⁰;    -   Y⁰ is optionally selected from the group consisting of        Q^(b)-Q^(ssss) and Q^(b)-Q^(ssssr) wherein Q^(ssss) is        (CH(R³⁸))_(r)—W⁵ and Q^(ssssr) is (CH(R³⁸))_(r)—W⁶, r is an        integer selected from 1 through 2, and W⁵ and W⁶ are        independently selected from the group consisting of 1,4-indenyl,        1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,        2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,        3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,        2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,        3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,        2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,        2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,        3,6-benzothiophenyl, 3,7-benzothiophenyl,        2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,        3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,        3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl,        2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,        3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,        2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,        1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,        3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,        2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,        3,5-benzoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,        1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,        1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,        2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,        2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,        3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,        4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,        1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,        1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,        3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,        3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,        4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,        3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,        4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and        4,8-cinnolinyl, and each carbon and hyrido containing nitrogen        member of the ring of the W⁵ and of the ring of the W⁶, other        than the points of attachment of W⁵ and W⁶, is optionally        substituted with one or more of the group consisting of R⁹, R¹⁰,        R¹¹, and R¹², with the provisos that Q^(b) is bonded to lowest        number substituent position of each W⁵, Q^(b) is bonded to        highest number substituent position of each W⁶, and        (CH(R³⁸))_(r) is bonded to E⁰.

In a more preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy,        hydroxy, amino, alkoxyamino, alkanoyl, haloalkanoyl, nitro,        lower alkylamino, alkylthio, aryl, aralkyl, cycloalkyl,        cycloalkylalkyl, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, alkyl, alkenyl, halo,        haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl,        alkylenylamino, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   B is optionally, with the proviso that R¹ and R² are selected        from the group consisting of a spacer pair and —W═X—Y=Z-,        Formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N;    -   B is optionally selected from the group consisting of hydrido,        trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl,        C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group        B is optionally substituted at any carbon up to and including 6        atoms from the point of attachment of B to A with one or more of        the group consisting of R³², R²³, R³⁴, R³⁵, and R³⁶;    -   B is selected from the group consisting of C3-C12 cycloalkyl and        C4 heterocyclyl, wherein each ring carbon is optionally        substituted with R³³, a ring carbon other than the ring carbon        at the point of attachment of B to A is optionally substituted        with oxo provided that no more than one ring carbon is        substituted by oxo at the same time, ring carbons and a nitrogen        adjacent to the carbon at the point of attachment are optionally        substituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent        to the R⁹ position and two atoms from the point of attachment is        optionally substituted with R¹⁰, a ring carbon or nitrogen        adjacent to the R¹³ position and two atoms from the point of        attachment are optionally substituted with R¹², a ring carbon        three atoms from the point of attachment and adjacent to the R¹⁰        position is optionally substituted with R¹¹, a ring carbon three        atoms from the point of attachment and adjacent to the R¹²        position is optionally substituted with R³³, and a ring carbon        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   B is optionally, with the proviso that R¹ and R² are selected        from the group consisting of a spacer pair and —W═X—Y=Z-, a        C5-C9 saturated heterocyclyl, wherein each ring carbon is        optionally substituted with R³³, a ring carbon other than the        ring carbon at the point of attachment of B to A is optionally        substituted with oxo provided that no more than one ring carbon        is substituted by oxo at the same time, ring carbons and        nitrogen adjacent to the carbon atom at the point of attachment        are optionally substituted with R⁹ or R¹³, a ring carbon or        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, a ring        carbon or nitrogen adjacent to the R¹³ position and two atoms        from the point of attachment is optionally substituted with R¹²,        a ring carbon or nitrogen three atoms from the point of        attachment and adjacent to the R¹⁰ position is optionally        substituted with R¹¹, a ring carbon or nitrogen three atoms from        the point of attachment and adjacent to the R¹² position is        optionally substituted with R³³, and a ring carbon or nitrogen        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido,        alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino,        alkylenedioxy, haloalkylthio, alkoxy, hydroxy, amino, lower        alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,        alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, aminoalkyl, carboalkoxy, carboxyalkyl, carboxy,        carboxamido, and cyano;    -   R⁹, R¹⁰, R¹¹, R¹², and R¹³ are optionally selected from the        group consisting of heteroaryl and heterocyclyl with the proviso        that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are substitutents for other than        B;    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is selected from the group consisting of O, S, C(O),        (R⁷)NC(O), (R⁷)NC(S), and N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, hydroxy,        halo, alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino,        aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,        hydroxyalkyl, alkoxyamino, thiol, and alkylthio;    -   R¹ and R² is optionally selected to be —W═X—Y=Z- wherein        —W═X—Y=Z- forms a ring selected from the group consisting of a        heteroaryl ring having from 5 through 6 contiguous members and        an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹), C(R¹²), N, N(R¹⁰), O, S and        a covalent bond with the provisos that W, X, Y, and Z can be        independently selected to be a covalent bond when one of W, X,        Y, and Z is selected from the group consisting of N, N(R¹⁰), O,        and S, no more than one of W, X, Y, and Z can be selected from        the group consisting of O and S, and no more than three of W, X,        Y, and Z can be selected from the group consisting of N and        N(R¹⁰);    -   R¹ and R² spacer pairs are independently optionally selected to        be taken together to form a spacer pair wherein the spacer pair        forms a linear moiety having from 3 through 6 contiguous atoms        connecting the points of bonding of said spacer pair members to        form a ring selected from the group consisting of a cycloalkenyl        ring having from 5 through 8 contiguous members and a partially        saturated heterocyclyl ring having from 5 through 8 contiguous        members, wherein said spacer pair is optionally substituted with        one or more of the group consisting of R⁹, R¹⁰, R¹¹, R¹², and        R¹³;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single bond        and (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1        through 2, (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are        integers independently selected from 0 through 3 and W⁰ is        selected from the group consisting of O, S, and N(R⁴¹), and        (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integers        independently selected from 0 through 1 and W²² is selected from        the group consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl,        1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,        1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,        2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,        1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,        2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,        2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,        3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,        2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,        3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,        2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the        proviso that Z⁰ is directly bonded to the pyridone ring;    -   R⁴¹ and R⁴² are independently selected from the group consisting        of hydrido, hydroxy, and amino;    -   Q is selected from the group consisting of hydrido, with the        proviso that Z⁰ is other than a covalent single bond, aryl, and        heteroaryl, wherein a carbon adjacent to the carbon at the point        of attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   K is CHR^(4a) wherein R^(4b) is selected from the group        consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,        alkylthioalkyl, and haloalkyl;    -   E⁰ is selected from the group consisting of a covalent single        bond, C(O)N(H), (H)NC(O), (R⁷)NS(O)₂, and S(O)₂N(R⁷);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² ⁹is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,        haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        aminoalkyl, and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and        C(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰        and R²¹ is hydroxy, amino, alkylamino, or dialkylamino at the        same time and that no more than one of R²³ and R²⁴ is hydroxy,        amino, alkylamino, or dialkylamino at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, alkyl, hydroxy, amino,        alkylamino and dialkylamino;    -   Q^(s) is selected from the group consisting of a single covalent        bond, (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1        through 4, and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d        are integers independently selected from 1 through 3 and W¹ is        selected from the group consisting of C(O)N(R¹⁴), (R¹⁴)NC(O),        S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the        provisos that R¹⁴ is selected from other than halo when directly        bonded to N and that (CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) are bonded        to E⁰;    -   R¹⁴ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   R³⁷ and R³⁸ are independently selected from the group consisting        of hydrido, alkyl, and haloalkyl;    -   R³⁸ is optionally selected from the group consisting of aroyl        and heteroaroyl;    -   Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is        (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are integers        independently selected from I through 2 and W² is CR^(4a)═CH        with the proviso that (CH(R¹⁴))_(e) is bonded to E⁰.

In an even more preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is selected from the group consisting of (R⁷)NC(O) and        N(R⁷);    -   R⁷is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of a covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,        alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl,        alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy,        carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,        alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy,        carboxy, carboxyalkyl, amidocarbonyl, halo, haloalkyl, and        cyano;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is optionally O, no more        than one of D⁵, D⁶, J⁵, and J⁶ is optionally S, one of D⁵, D⁶,        J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵ and J⁶        are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos        that no more than one of R²⁰ and R²¹ is hydroxy at the same time        and that no more than one of R²³ and R²⁴ is hydroxy at the same        time;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, alkyl, and hydroxy;    -   Q^(s) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In another even more preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is optionally selected from the group consisting of hydrido,        C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl,        wherein each member of group B is optionally substituted at any        carbon up to and including 6 atoms from the point of attachment        of B to A with one or more of the group consisting of R³², R³³,        R³⁴, R³⁵, and R³⁶;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is selected from the group consisting of (R⁷)NC(O) and        N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,        alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl,        alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy,        carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,        alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, hydroxyalkyl, alkylenylamino,        carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo,        haloalkyl, and cyano;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        alkylenylamino, and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no more than        one of R²⁰ and R²¹ is hydroxy at the same time and that no more        than one of R²³ and R²⁴ is hydroxy at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, alkyl, and hydroxy;    -   Q^(s) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In still another even more preferred embodiment of compounds of FormulaI or a pharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is selected from the group consisting of C3-C7 cycloalkyl and        C4 heterocyclyl, wherein each ring carbon is optionally        substituted with R³³, a ring carbon other than the ring carbon        at the point of attachment of B to A is optionally substituted        with oxo provided that no more than one ring carbon is        substituted by oxo at the same time, ring carbons and a nitrogen        adjacent to the carbon at the point of attachment are optionally        substituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent        to the R⁹ position and two atoms from the point of attachment is        optionally substituted with R¹⁰, a ring carbon or nitrogen        adjacent to the R¹³ position and two atoms from the point of        attachment is optionally substituted with R¹², a ring carbon        three atoms from the point of attachment and adjacent to the R¹⁰        position is optionally substituted with R¹¹, a ring carbon three        atoms from the point of attachment and adjacent to the R¹²        position is optionally substituted with R²³, and a ring carbon        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,        alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl,        alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy,        carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,        alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl,. hydroxyalkyl, alkylenylamino,        carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo,        haloalkyl, and cyano;    -   R³³ and R³⁴ are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino,        alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,        alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl        amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is selected from the group consisting of (R⁷)NC(O) and        N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵ , and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        alkylenylamino, and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos        that no more than one of R²⁰ and R²¹ is hydroxy at the same time        and that no more than one of R²³ and R²⁴ is hydroxy at the same        time;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, alkyl, and hydroxy;    -   Q^(s) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In a further even more preferred embodiment of compounds of Formula l ora pharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K is O, no more than one of D¹, D²,        J¹, J² and K¹ is S, one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   B is optionally selected from the group consisting of hydrido,        C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl,        wherein each member of group B is optionally substituted at any        carbon up to and including 6 atoms from the point of attachment        of B to A with one or more of the group consisting of R³², R³³,        R³⁴, R³⁵, and R³⁶;    -   B is selected from the group consisting of C3-C7 cycloalkyl and        C4-C6 saturated heterocyclyl, wherein each ring carbon is        optionally substituted with R³³, a ring carbon other than the        ring carbon at the point of attachment of B to A is optionally        substituted with oxo provided that no more than one ring carbon        is substituted by oxo at the same time, ring carbons and        nitrogen adjacent to the carbon atom at the point of attachment        are optionally substituted with R⁹ or R¹³, a ring carbon or        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, a ring        carbon or nitrogen adjacent to the R¹³ position and two atoms        from the point of attachment is optionally substituted with R¹²,        a ring carbon or nitrogen three atoms from the point of        attachment and adjacent to the R¹⁰ position is optionally        substituted with R¹¹, a ring carbon or nitrogen three atoms from        the point of attachment and adjacent to the R¹² position is        optionally substituted with R³³, and a ring carbon or nitrogen        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido,        alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino,        alkylenedioxy, haloalkylthio, heteroaryl, heterocyclyl, alkoxy,        hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,        alkylsulfonyl, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,        haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxyalkyl,        carboxy, carboxamido, and cyano;    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is selected from the group consisting of (R⁷)NC(O) and        N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alky    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkxy and haloalkyl;    -   Ψ is NH;    -   X⁰ is selected from the group consisting of hydrido, alkyl,        cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,        alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,        hydroxyalkyl, alkoxyamino, thiol, and alkylthio;    -   R¹ and R² are taken together to be —W═X—Y=Z- wherein —W═X—Y=Z-        forms a ring selected from the group consisting of a heteroaryl        ring having from 5 through 6 contiguous members and an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹), C(R¹²), N, N(R¹⁰), O, S and        a covalent bond with the provisos that W, X, Y, and Z can be        independently selected to be a covalent bond when one of W, X,        Y, and Z is selected from the group consisting of N, N(R¹⁰), O,        and S, no more than one of W, X, Y, and Z is optionally selected        from the group consisting of O and S, and no more than three of        W, X, Y, and Z can be selected from the group consisting of N        and N(R¹⁰);    -   R¹ and R² spacer pair is optionally selected to be taken        together to form a spacer pair wherein the spacer pair forms a        linear moiety having from 3 through 6 contiguous atoms        connecting the points of bonding of said spacer pair members to        form a ring selected from the group consisting of a cycloalkenyl        ring having from 5 through 8 contiguous members and a partially        saturated heterocyclyl ring having from 5 through 8 contiguous        members, wherein said spacer pair is optionally substituted with        one or more of the group consisting of R⁹, R¹⁰, R¹¹, R¹², and        R¹³;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,        haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        aminoalkyl, and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and        C(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰        and R²¹ is hydroxy, amino, alkylamino, or dialkylamino at the        same time and that no more than one of R²³ and R²⁴ is hydroxy,        amino, alkylamino, or dialkylamino at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, alkyl, hydroxy, amino,        alkylamino and dialkylamino;    -   Q^(s) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CR₂.

In a most preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetarido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is N(R⁷);    -   R⁷ is selected from the group consisting of hydrido and alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹ , the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo,. haloalkyl,        haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower        alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl,        halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl,        carboxyamido, and cyano;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(b)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido and alkyl;    -   Q^(s) is CH₂.

In another most preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is optionally selected from the group consisting of hydrido,        C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl,        wherein each member of group B is optionally substituted at any        carbon up to and including 6 atoms from the point of attachment        of B to A with one or more of the group consisting of R³², R³³,        R³⁴, R³⁵, and R³⁶;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is N(R⁷);    -   R⁷ is selected from the group consisting of hydrido and alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹², and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,        haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower        alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl,        halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl,        carboxyamido, and cyano;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and        C(NR²⁵)NR²³R²⁴;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido and alkyl;    -   Q^(S) is CH₂.

In still another most preferred embodiment of compounds of Formula I ora pharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is selected from the group consisting of C3-C7 cycloalkyl and        C4 heterocyclyl, wherein each ring carbon is optionally        substituted with R³³, a ring carbon other than the ring carbon        at the point of attachment of B to A is optionally substituted        with oxo provided that no more than one ring carbon is        substituted by oxo at the same time, ring carbons and nitrogens        adjacent to the carbon at the point of attachment are optionally        substituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent        to the R⁹ position and two atoms from the point of attachment is        optionally substituted with R¹⁰, a ring carbon or nitrogen        adjacent to the R¹³ position and two atoms from the point of        attachment is optionally substituted with R¹², a ring carbon        three atoms from the point of attachment and adjacent to the R¹⁰        position is optionally substituted with R¹¹, a ring carbon three        atoms from the point of attachment and adjacent to the R¹²        position is optionally substituted with R³³, and a ring carbon        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,        haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower        alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl,        halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl,        carboxyamido, and cyano;    -   R³³ and R³⁴ are independently selected from the group consisting        of hydrido, amidino, guanidino, alkoxy, hydroxy, amino,        alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl,        monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo,        haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,        carboxamido, and cyano;    -   R³³ is optionally Q^(b);    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the croup consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   R¹ and X⁰ are independently selected from the group consisting        of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,        hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,        alkoxyamino, haloalkyl, haloalkoxy, and halo;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of aryl and heteroaryl        wherein a carbon adjacent to the carbon at the point of        attachment is optionally substituted by R⁹, the other carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R¹³, a carbon adjacent to R⁹ and two atoms from        the carbon at the point of attachment is optionally substituted        by R¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon        at the point of attachment is optionally substituted by R¹³, and        any carbon adjacent to both R¹⁰ and R¹² is optionally        substituted by R¹¹;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,        alkylenylamino, and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido and alkyl;    -   Q^(S) is CH₂.

In a further most preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

-   -   J is O;    -   B is the Formula (V):        wherein D¹, D², J¹, J² and K¹ are independently selected from        the group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, no more than        one of D¹, D², J¹, J² and K¹ is O, no more than one of D¹, D²,        J¹, J² and K¹ is S one of D¹, D², J¹, J² and K¹ must be a        covalent bond when two of D¹, D², J¹, J² and K¹ are O and S, and        no more than four of D¹, D², J¹, J² and K¹ are N;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, acetamido, haloacetamido, amidino,        guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower        alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,        dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,        hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and        Q^(b);

B is optionally selected from the group consisting of hydrido, C2-C8alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

-   -   B is selected from the group consisting of C3-C7 cycloalkyl and        C4-C6 saturated heterocyclyl, wherein each ring carbon is        optionally substituted with R³³, a ring carbon other than the        ring carbon at the point of attachment of B to A is optionally        substituted with oxo provided that no more than one ring carbon        is substituted by oxo at the same time, ring carbons and        nitrogen adjacent to the carbon atom at the point of attachment        are optionally substituted with R⁹ or R¹³, a ring carbon or        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, a ring        carbon or nitrogen adjacent to the R¹³ position and two atoms        from the point of attachment is optionally substituted with R¹²,        a ring carbon or nitrogen three atoms from the point of        attachment and adjacent to the R¹⁰ position is optionally        substituted with R¹¹, a ring carbon or nitrogen three atoms from        the point of attachment and adjacent to the R¹² position is        optionally substituted with R³³, and a ring carbon or nitrogen        four atoms from the point of attachment and adjacent to the R¹¹        and R³³ positions is optionally substituted with R³⁴;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, guanidino, lower        alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,        amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,        haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,        alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, lower        alkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl        amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl,        halo, haloalkyl, carboalkoxy, carboxy, carboxyalkyl,        carboxyamido, and cyano;    -   A is selected from the group consisting of single covalent bond        and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected        from 0 through 1, pa is an integer selected from 0 through 3,        and W⁷ is N(R⁷);    -   R⁷ is selected from the group consisting of hydrido, hydroxy and        alkyl;    -   R¹⁵ is selected from the group consisting of hydrido, halo,        alkyl, and haloalkyl;    -   Ψ is NH;    -   X⁰ is selected from the group consisting of hydrido, alkyl,        cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,        alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,        hydroxyalkyl, alkoxyamino, thiol, and alkylthio;    -   R¹ and R² are taken together to be —W═X—Y=Z- wherein —W═X—Y=Z-        forms a ring selected from the group consisting of a heteroaryl        ring having 6 contiguous members and an aryl;    -   W, X, Y, and Z are independently selected from the group        consisting of C(R⁹), C(R¹⁰), C(R¹¹), C(R¹²), and N;    -   K is CH₂;    -   E⁰ is C(O)N(H);    -   Y⁰ is formula (IV):        wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the        group consisting of C, N, O, S and a covalent bond with the        provisos that no more than one is a covalent bond, K² is C, no        more than one of D⁵, D⁶, J⁵, and J⁶ is O, no more than one of        D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶, J⁵, and J⁶ must be a        covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no        more than four of D⁵, D⁶, J⁵, and J⁶ are N, with the provisos        that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected to        maintain the tetravalent nature of carbon, trivalent nature of        nitrogen, the divalent nature of sulfur, and the divalent nature        of oxygen;    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy,        haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino,        alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,        alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(b)        wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and        C(NR²⁵)NR²³R²⁴;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido and alkyl;    -   Q^(S) is CH₂.

In a preferred specific embodiment of Formula I, compounds have theFormula I-S:

or a pharmaceutically acceptable salt thereof, wherein;

-   -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, carboxy,        methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy,        propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,        trifluoroacetamido, nitro, aminomethyl, 1-aminoethyl,        2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,        methylthio, ethylthio, isopropylthio, trifluoromethylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,        propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,        1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,        2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,        methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and        Q^(b);    -   B is selected from the group consisting of hydrido,        trimethylsilyl, ethyl, 2-propenyl, 2-propynyl, propyl,        isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl,        tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,        3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,        1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl,        3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,        2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,        3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl,        4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,        1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,        3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,        1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl,        3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,        3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl,        1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl,        1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,        1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl,        1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl,        1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl,        3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl,        2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl,        1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl,        1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl,        1-methyl-3-heptynyl, 1-methyl-heptenyl, 1-methyl-5-heptenyl,        1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl,        1-methyl-4-heptynyl, 1-methyl-5-heptynyl, 3-octyl,        1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethylhexenyl,        1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl,        1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl,        1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl,        1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl,        1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2,2-trifluoroethyl,        2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,        4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and        3,3,3-trifluoropropyl, wherein each member of group B is        optionally substituted at any carbon up to and including 5 atoms        from the point of attachment of B to A with one or more of the        group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶.    -   B is optionally selected from the group consisting of        cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl,        azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl,        thiaetan-3-yl, cyclopentyl, cyclohexyl, adamantyl, norbornyl,        3-trifluoromethylnorbornyl, bicyclo[3.1.0]hexan-6-yl,        cycloheptyl, and cyclooctyl, wherein each ring carbon is        optionally substituted with R³³, ring carbons or a nitrogen        adjacent to the carbon atom at the point of attachment are        optionally substituted with R⁹ or R¹³, a ring carbon or a        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, and a        ring carbon or a nitrogen adjacent to the R¹³ position and two        atoms from the point of attachment is optionally substituted        with R¹²;    -   R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the        group consisting of hydrido, amidino, guanidino, carboxy,        carboxymethyl, methyl, ethyl, isopropyl, propyl, methoxy,        ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,        ethoxyamino, acetamido, trifluoroacetamido, nitro, aminomethyl,        1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,        N-ethylamino, methylthio, ethylthio, isopropylthio,        trifluoromethylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,        trifluoromethoxy, 1,1,2,2-tetrafluoroetboxy, fluoro, chloro,        bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl,        pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,        2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,        methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;    -   A is selected from the group consisting of single covalent bond,        O, S, NH, N(CH₃), N(OH), C(O), CH₂, CH₃CH, CF₃CH, NHC(O),        N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CF₃CC(O), C(O)CCH₃, C(O)CCF₃,        CH₂C(O), (O)CCH₂, CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, CF₃CHCH₂,        CH₃CC(O)CH₂, CF₃CC(O)CH₂, CH₂C(O)CCH₃, CH₂C(O)CCF₃, CH₂CH₂C(O),        and CH₂(O)CCH₂;    -   A is optionally selected from the group consisting of CH₂N(CH₃),        CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso        that B is hydrido;    -   R¹ and X^(o) are independently selected from the group        consisting of hydrido, hydroxy, amino, thiol, amidino,        hydroxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl,        methylamino, dimethylamino, cyano, methyl, ethyl, isopropyl,        propyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, methoxy, ethoxy, propoxy,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,        ethoxyamino, methylthio, ethylthio, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, CH₂, CH₂CH₂, CH(OH), CH(NH₂), CH₂CH(OH),        CH₂CHNH₂, CH(OH)CH₂, and CH(NH₂)CH₂;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl,        1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl,        1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl,        2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl,        3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,        1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl,        1,2,3-triazin-4-yl, and 1,2,3-triazin-5-yl, wherein a carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R⁹, the other carbon adjacent to the carbon at        the point of attachment is optionally substituted by R¹³, a        carbon adjacent to R⁹ and two atoms from the carbon at the point        of attachment is optionally substituted by R¹⁰, a carbon        adjacent to R¹³ and two atoms from the carbon at the point of        attachment is optionally substituted by R¹², and any carbon        adjacent to both R¹⁰ and R¹² is optionally substituted by R¹¹;    -   K is CHR^(4a) wherein R^(4a) is selected from the group        consisting of methyl, ethyl, propyl, isopropyl, hydroxymethyl,        1-hydroxyethyl, methoxymethyl, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoromethyl, methylthiomethyl, and        hydrido;    -   E⁰ is a covalent single bond, C(O)N(H), (H)NC(O), and S(O)₂N(H);    -   Y⁰ is selected from the group of formulas consisting of:    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, methyl, ethyl, isopropyl, propyl,        amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,        propoxy, hydroxy, amnino, methoxyamino, ethoxyamino,        aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino,        dimethylamino, N-ethylamino, methylthio, ethylthio,        isopropylthio, trifluoromethylthio, methylsulfinyl,        ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,        propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,        1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be);    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴ and        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that no more than one        of R²⁰ and R²¹ is hydroxy, N-methylamino, and N,N-dimethylamino        at the same time and that no more than one of R²³ and R²⁴ is        hydroxy, N-methylamino, and N,N-dimethylamino at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, methyl, ethyl, propyl, butyl,        isopropyl, hydroxy, 2-aminoethyl, 2-(N-methylamino)ethyl, and        2-(N,N-dimethylamino)ethyl;    -   Q is selected from the group consisting of a single covalent        bond, CH₂, CH₂CH₂, CH₃CH, CF₃CH, CH₃CHCH₂, CF₃CHCH₂, CH₂(CH₃)CH,        CH═CH, CF═CH, C(CH₃)═CH, CH═CHCH₂, CF═CHCH₂, C(CH₃)═CHCH₂,        CH₂CH═CH, CH₂CF═CH, CH₂C(CH₃)═CH, CH₂CH═CHCH₂, CH₂CF═CHCH₂,        CH₂C(CH₃)═CHCH₂, CH₂CH═CHCH₂CH₂, CH₂CF═CHCH₂CH₂, and        CH₂C(CH₃)═CHCH₂CH₂.

In a more preferred specific embodiment of Formula I, compounds have theFormula I-MPS wherein B is an aromatic:

-   -   (I-MPS wherein B is aromatic)        or a pharmaceutically acceptable salt thereof, wherein;    -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, carboxy,        methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,        methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,        N-methylamino, dimethylamino, N-ethylamino, methylthio,        ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,        bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,        ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,        N,N-dimethylamidocarbonyl, cyano, and Q^(b);    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O),        C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;    -   R¹ and X^(o) are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,        aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano,        methyl, ethyl, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, methoxyamino, methylthio, ethylthio,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and        bromo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,        4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and        1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at        the point of attachment is optionally substituted by R⁹, the        other carbon adjacent to the carbon at the point of attachment        is optionally substituted by R¹³, a carbon adjacent to R⁹ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two        atoms from the carbon at the point of attachment is optionally        substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²        is optionally substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,        methylthio, ethylthio, isopropylthio, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,        methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, methoxyamino, ethoxyamino, acetamido,        trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,        N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,        amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,        2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,        amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,        fluoro, chloro, bromo, and cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos        that no more than one of R²⁰ and R²¹ is hydroxy at the same time        and that no more than one of R²³ and R²⁴ is hydroxy at the same        time;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, methyl, ethyl, propyl, butyl,        isopropyl, and hydroxy;    -   Q^(S) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In another more preferred specific embodiment of Formula I, compoundshave the Formula I-MPS wherein B is a non-cyclic substituent:

(I-MPS wherein B is a non-cyclic substituent) or a pharmaceuticallyacceptable salt thereof, wherein;

-   -   B is selected from the group consisting of hydrido, ethyl,        2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,        3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,        2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,        2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,        1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,        1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,        2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,        3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl,        4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,        1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,        3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,        1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl,        3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,        3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl,        1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl,        1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,        1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl,        1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl,        1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,        2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,        4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and        3,3,3-trifluoropropyl, wherein each member of group B is        optionally substituted at any carbon up to and including 5 atoms        from the point of attachment of B to A with one or more of the        group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, carboxy,        methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,        methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,        N-methylamino, dimethylamino, N-ethylamino, methylthio,        ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,        bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,        ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,        N,N-dimethylamidocarbonyl, cyano, and Q^(b);    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O),        C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;    -   A is optionally selected from the group consisting of CH₂N(CH₃),        CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso        that B is hydrido;    -   R¹ and X^(o) are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,        aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano,        methyl, ethyl, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, methoxyamino, methylthio, ethylthio,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and        bromo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,        4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and        1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at        the point of attachment is optionally substituted by R⁹, the        other carbon adjacent to the carbon at the point of attachment        is optionally substituted by R¹³, a carbon adjacent to R⁹ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two        atoms from the carbon at the point of attachment is optionally        substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²        is optionally substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,        methylthio, ethylthio, isopropylthio, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,        methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, methoxyamino, ethoxyamino, acetamido,        trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,        N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,        amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,        2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,        amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,        fluoro, chloro, bromo, and cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be),        wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no more than        one of R²⁰ and R²¹ is hydroxy at the same time and that no more        than one of R²³ and R²⁴ is hydroxy at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, methyl, ethyl, propyl, butyl,        isopropyl, and hydroxy;    -   Q^(S) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In still another more preferred specific embodiment of Formula I,compounds have the Formula I-MPS wherein B is a non-aromatic cyclicsubstituent:

(I-MPS wherein B is a non-aromatic cyclic substituent) or apharmaceutically acceptable salt thereof, wherein;

-   -   B is optionally selected from the group consisting of        cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl,        azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl,        cyclohexyl, norbornyl, bicyclo[3.1.0]hexan-6-yl, and        cycloheptyl, wherein each ring carbon is optionally substituted        with R³³, ring carbons or a nitrogen adjacent to the carbon atom        at the point of attachment is optionally substituted with R⁹ or        R¹³, a ring carbon or nitrogen adjacent to the R⁹ position and        two atoms from the point of attachment is optionally substituted        with R¹⁰, and a ring carbon or nitrogen adjacent to the R¹³        position and two atoms from the point of attachment is        optionally substituted with R¹²;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, amidino, guanidino, carboxy, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,        methylthio, ethylthio, isopropylthio, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,        methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, methoxyamino, ethoxyamino, acetamido,        trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,        N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,        amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,        2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,        amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,        fluoro, chloro, bromo, and cyano;    -   R³³ are independently selected from the group consisting of        hydrido, amidino, guanidino, carboxy, methoxy, ethoxy,        isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,        acetamido, trifluoroacetamido, N-methylamino, dimethylamino,        N-ethylamino, methylthio, ethylthio, isopropylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,        1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,        methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, Q^(b);    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O),        C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;    -   R¹ and X^(o) are independently selected from the group        consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,        aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano,        methyl, ethyl, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, methoxyamino, methylthio, ethylthio,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and        bromo;    -   R² is Z⁰-Q;    -   Z⁰ is selected from the group consisting of covalent single        bond, O, S, NH, and CH₂;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,        4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        S-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and        1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at        the point of attachment is optionally substituted by R⁹, the        other carbon adjacent to the carbon at the point of attachment        is optionally substituted by R¹³, a carbon adjacent to R⁹ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two        atoms from the carbon at the point of attachment is optionally        substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²        is optionally substituted by R¹¹;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)        wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos        that no more than one of R²⁰ and R²¹ is hydroxy at the same time        and that no more than one of R²³ and R²⁴ is hydroxy at the same        time;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, methyl, ethyl, propyl, butyl,        isopropyl, and hydroxy;    -   Q^(S) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

In a further even more preferred embodiment of compounds of Formula I,compounds have the Formula I-FARMPS wherein there are two fused aromaticrings:

or a pharmaceutically acceptable salt thereof, wherein;

-   -   B is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,        4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and        1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at        the point of attachment is optionally substituted by R³², the        other carbon adjacent to the carbon at the point of attachment        is optionally substituted by R³⁶, a carbon adjacent to R³² and        two atoms from the carbon at the point of attachment is        optionally substituted by R³³, a carbon adjacent to R³⁶ and two        atoms from the carbon at the point of attachment is optionally        substituted by R³⁵, and any carbon adjacent to both R³³ and R³⁵        is optionally substituted by R³⁴;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, carboxy,        methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,        methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,        N-methylamino, dimethylamino, N-ethylamino, methylthio,        ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,        bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,        ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,        N,N-dimethylamidocarbonyl, cyano, and Q^(b);    -   B is selected from the group consisting of hydrido, ethyl,        2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,        3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,        2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,        2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,        1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,        1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,        2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,        3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl,        4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,        1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,        3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,        1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl,        3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,        3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl,        1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl,        1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,        1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl,        1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl,        1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,        2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,        4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and        3,3,3-trifluoropropyl, wherein each member of group B is        optionally substituted at any carbon up to 5 and including 5        atoms from the point of attachment of B to A with one or more of        the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;    -   B is optionally selected from the group consisting of        cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl,        azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl,        cyclohexyl, norbornyl, 7-oxabicyclo[2.2.1]heptan-2-yl,        bicyclo[3.1.0]hexan-6-yl, cycloheptyl, 2-morpholinyl,        3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl,        1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,        1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl,        4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl,        4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,        2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,        2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring        carbon is optionally substituted with R³³, a ring carbon and        nitrogen atoms adjacent to the carbon atom at the point of        attachment is optionally substituted with R⁹ or R¹³, a ring        carbon or nitrogen atom adjacent to the R⁹ position and two        atoms from the point of attachment is optionally substituted        with R¹⁰, and a ring carbon or nitrogen atom adjacent to the R¹³        position and two atoms from the point of attachment is        optionally substituted with R¹²;    -   R⁹ and R¹¹ are independently selected from the group consisting        of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl,        isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,        N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio,        ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,        trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,        bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,        N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl,        ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,        hydroxy, amino, methoxyamino, ethoxyamino, acetamido,        trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,        N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,        amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,        2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,        amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,        fluoro, chloro, bromo, and cyano;    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O),        C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;    -   A is optionally selected from the group consisting of CH₂N(CH₃),        CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso        that B is hydrido;    -   X^(o) is selected from the group consisting of hydrido, hydroxy,        amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl,        methylamino, dimethylamino, cyano, methyl, ethyl,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,        methoxyamino, methylthio, ethylthio, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;    -   W, X, Y, and Z are independently selected from the group        consisting of CH, N, CF, CCl, C—CN, C—CH₃, C—CH₂CH₃, C—NH₂,        C—CH₂NH₂, C—CH₂NHCH₃, C—NHCH₃, C—N(CH₃)₂, C—CH(NH₂)CH₃,        C—CH₂CH₂NH₂, C—NHOCH₃, C—NHOCH₂CH₃, C—C(NH)NH₂, C—C(NOH)NH₂,        C—OH, C—CH₂OH, C—CH₂CH₂OH, C—CH(OH)CH₃, C—OCH₃, C—OCH₂CH₃,        C—CO₂H, C—CO₂CH₃, C—C(O)NH₂, C—C(O)NHCH₃, C—C(O)NH(CH₃)₂,        C—CH₂CO₂H, C—SO₂NH₂, C—SO₂NHCH₃, C—NH(O)CCH₃, and C—NH(O)CCF₃;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be),        wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and        N(R²⁶)C(NR²⁵)N(R²³)(R²⁴) with the provisos that no more than one        of R²⁰ and R²¹ is hydroxy at the same time and that no more than        one of R²³ and R²⁴ is hydroxy at the same time;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, methyl, ethyl, propyl, butyl,        isopropyl, and hydroxy;    -   Q^(S) is selected from the group consisting of a single covalent        bond, CH₂, and CH₂CH₂.

The more preferred specific embodiment (I-MPS) and (I-FARMPS) compoundsof the present invention having the Formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

-   -   Y⁰ is selected from the group of formulas consisting of:    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, methyl, ethyl, isopropyl, propyl,        carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy,        propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,        2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,        methylthio, ethylthio, isopropylthio, trifluoromethylthio,        methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,        1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,        1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,        and cyano;    -   R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no more        than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b)        is Q^(be).

In a most preferred specific embodiment of Formula I, compounds have theFormula I-EMPS wherein B is an aromatic:

-   -   (I-EMPS wherein B is aromatic)        or a pharmaceutically acceptable salt thereof, wherein;    -   B is the Formula:    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, methyl, ethyl,        methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino,        methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy,        cyano, and Q^(b);    -   A is selected from the group consisting-of single covalent bond,        NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;    -   X^(o) is selected from the group consisting of hydrido, hydroxy,        amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,        hydroxymethyl, and fluoro;    -   R¹ is selected from the group consisting of hydrido, hydroxy,        amino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl,        methoxy, methylthio, trifluoromethoxy, fluoro, and chloro;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,        2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the        carbon at the point of attachment is optionally substituted by        R⁹, the other carbon adjacent to the carbon at the point of        attachment is optionally substituted by R¹³, a carbon adjacent        to R⁹ and two atoms from the carbon at the point of attachment        is optionally substituted by R¹⁰, a carbon adjacent to R¹³ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹², and any carbon adjacent to both        R¹⁰ and R¹² is optionally substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,        amino, N-methylamino, N,N-dimethylamino, methylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,        chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,        guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,        carboxymethyl, amino, acetamido, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,        aminomethyl, N-methylamino, dimethylamino, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        methoxycarbonyl, fluoro, chloro, bromo, and cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹ and        C(NR²⁵)NR²³R²⁴, with the proviso that said Q^(b) group is bonded        directly to a carbon atom;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, methyl, and ethyl;    -   Q^(S) is CH₂.

In another most preferred specific embodiment of Formula I, compoundshave the Formula I-EMPS wherein B is a non-cyclic substituent:

(I-EMPS wherein B is a non-cyclic substituent) or a pharmaceuticallyacceptable salt thereof, wherein;

-   -   B is selected from the group consisting of hydrido, ethyl,        2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,        2-butynyl, sec-butyl, tent-butyl, isobutyl, 2-methylpropenyl,        1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl,        2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,        3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,        1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,        1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl,        2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl,        3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl,        1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl,        1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl,        3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,        1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,        2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,        4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and        3,3,3-trifluoropropyl, wherein each member of group B is        optionally substituted at any carbon up to and including 5 atoms        from the point of attachment of B to A with one or more of the        group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, methyl, ethyl,        methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino,        methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy,        cyano, and Q^(b);    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;    -   A is optionally selected from the group consisting of CH₂N(CH₃),        CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso        that B is hydrido;    -   X^(o) is selected from the group consisting of hydrido, hydroxy,        amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,        hydroxymethyl, and fluoro;    -   R¹ is selected from the group consisting of hydrido, hydroxy,        amino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl,        methoxy, methylthio, trifluoromethoxy, fluoro, and chloro;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,        2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the        carbon at the point of attachment is optionally substituted by        R⁹, the other carbon adjacent to the carbon at the point of        attachment is optionally substituted by R¹³, a carbon adjacent        to R⁹ and two atoms from the carbon at the point of attachment        is optionally substituted by R¹⁰, a carbon adjacent to R¹³ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹², and any carbon adjacent to both        R¹⁰ and R¹² is optionally substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,        amino, N-methylamino, N,N-dimethylamino, methylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,        chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,        guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,        carboxymethyl, amino, acetamido, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,        aminomethyl, N-methylamino, dimethylamino, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        methoxycarbonyl, fluoro, chloro, bromo, and cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹,        C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso        that said Q^(b) group is bonded directly to a carbon atom;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, methyl, and ethyl;    -   Q^(S) is CH₂;

In still another most preferred specific embodiment of Formula I,compounds have the Formula I-EMPS wherein B is a non-aromatic cyclicsubstituent:

(I-EMPS wherein B is a non-aromatic cyclic substituent) or apharmaceutically acceptable salt thereof, wherein;

-   -   B is optionally selected from the group consisting of        cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-3-yl,        thiaetan-3-yl, cyclopentyl, and cyclohexyl, wherein each ring        carbon is optionally substituted with R³³, ring carbons or a        nitrogen adjacent to the carbon atom at the point of attachment        is optionally substituted with R⁹ or R¹³, a ring carbon or        nitrogen adjacent to the R⁹ position and two atoms from the        point of attachment is optionally substituted with R¹⁰, and a        ring carbon or nitrogen adjacent to the R¹³ position and two        atoms from the point of attachment is optionally substituted        with R¹²;    -   R³³ are independently selected from the group consisting of        hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy,        hydroxy, carboxy, amino, N-methylamino, dimethylamino,        methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano, and        Q^(b);    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;    -   X^(o) is selected from the group consisting of hydrido, hydroxy,        amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,        hydroxymethyl, and fluoro;    -   R¹ is selected from the group consisting of hydrido, hydroxy,        amino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl,        methoxy, methylthio, trifluoromethoxy, fluoro, and chloro;    -   R² is Z⁰-Q;    -   Z⁰ is a covalent single bond;    -   Q is selected from the group consisting of phenyl, 2-thienyl,        2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,        2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the        carbon at the point of attachment is optionally substituted by        R⁹, the other carbon adjacent to the carbon at the point of        attachment is optionally substituted by R¹³, a carbon adjacent        to R⁹ and two atoms from the carbon at the point of attachment        is optionally substituted by R¹⁰, a carbon adjacent to R¹³ and        two atoms from the carbon at the point of attachment is        optionally substituted by R¹², and any carbon adjacent to both        R¹⁰ and R¹² is optionally substituted by R¹¹;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,        amino, N-methylamino, N,N-dimethylamino, methylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,        chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,        guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,        carboxymethyl, amino, acetamido, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,        aminomethyl, N-methylamino, dimethylamino, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        methoxycarbonyl, fluoro, chloro, bromo, and cyano;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹ and        C(NR²⁵)NR²³R²⁴, with the proviso that said Q^(b) group is bonded        directly to a carbon atom;    -   R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the        group consisting of hydrido, methyl, and ethyl;    -   Q^(S) is CH₂.

In a further most preferred embodiment of compounds of Formula I,compounds have the Formula I-FARMPS wherein there are two fused aromaticrings:

or a pharmaceutically acceptable salt thereof, wherein;

-   -   B is selected from the group consisting of phenyl, 2-thienyl,        3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,        2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,        2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a carbon        adjacent to the carbon at the point of attachment is optionally        substituted by R³², the other carbon adjacent to the carbon at        the point of attachment is optionally substituted by R³⁶, a        carbon adjacent to R³² and two atoms from the carbon at the        point of attachment is optionally substituted by R³³, a carbon        adjacent to R³⁶ and two atoms from the carbon at the point of        attachment is optionally substituted by R³⁵, and any carbon        adjacent to both R³³ and R³⁵ is optionally substituted by R³⁴;    -   R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the        group consisting of hydrido, amidino, guanidino, methyl, ethyl,        methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino,        methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,        2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,        N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy,        cyano, and Q^(b);    -   B is selected from the group consisting of hydrido, ethyl,        2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,        2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl,        1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl,        2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,        3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,        1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,        1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl,        2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl,        3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl,        1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl,        1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl,        3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,        1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,        2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,        4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and        3,3,3-trifluoropropyl, wherein each member of group B is        optionally substituted at any carbon up to and including 5 atoms        from the point of attachment of B to A with one or more of the        group consisting of R³² R³³, R³⁴, R³⁵, and R³⁶;    -   B is optionally selected from the group consisting of        cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-3-yl,        thiaetan-3-yl, cyclopentyl, cyclohexyl, 1-pyrrolidinyl,        2-pyrrolidinyl, 3-pyrrolidinyl, 2-tetrahydrofuranyl,        3-tetrahydrofuranyl, 2-tetrahydrothienyl, and        3-tetrahydrothienyl, wherein each ring carbon is optionally        substituted with R³³, a ring carbon and nitrogen atoms adjacent        to the carbon atom at the point of attachment is optionally        substituted with R⁹ or R¹³, a ring carbon or nitrogen atom        adjacent to the R⁹ position and two atoms from the point of        attachment is optionally substituted with R¹⁰, and a ring carbon        or nitrogen atom adjacent to the R¹³ position and two atoms from        the point of attachment is optionally substituted with R¹²;    -   R⁹, R¹¹, and R¹³ are independently selected from the group        consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,        amino, N-methylamino, N,N-dimethylamino, methylthio,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,        chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,        N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,        amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;    -   R¹⁰ and R¹² are independently selected from the group consisting        of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,        guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,        hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,        carboxymethyl, amino, acetamido, trifluoromethyl,        pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,        aminomethyl, N-methylamino, dimethylamino, amidosulfonyl,        N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,        methoxycarbonyl, fluoro, chloro, bromo, and cyano;    -   A is selected from the group consisting of single covalent bond,        NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;    -   A is optionally selected from the group consisting of CH₂N(CH₃),        CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso        that B is hydrido;    -   X^(o) is selected from the group consisting of hydrido, hydroxy,        amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,        hydroxymethyl, and fluoro;    -   W and Z are independently selected from the group consisting of        CH, N, CF, CCl, C—CN, C—NH₂, C—CH₂NH₂, C—NHCH₃, C—OH, C—CH₂OH,        C—CO₂H, and C—C(O)NH₂;    -   X and Y are independently selected from the group consisting of        CH, N, CF, C—CN, C—CH₃, C—NH₂, C—CH₂NH₂, C—CH₂NHCH₃, C—NHCH₃,        C—CH(NH₂)CH₃, C—CH₂CH₂NH₂, C—NHOCH₃, C—C(NH)NH₂, C—C(NOH)NH₂,        C—OH, C—CH₂OH, C—CH₂CH₂OH, C—CH(OH)CH₃, C—OCH₃, C—CO₂H,        C—C(O)NH₂, C—C(O)NHCH₃, C—CH₂CO₂H, and C—SO₂NH₂;    -   Q^(b) is selected from the group consisting of NR²⁰R²¹        C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the proviso        that said Q^(b) group is bonded directly to a carbon atom;    -   R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from        the group consisting of hydrido, methyl, and ethyl;    -   Q^(S) is CH₂.

The most preferred specific embodiment (I-EMPS) compounds of the presentinvention having the Formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

-   -   Y⁰ is selected from the group of formulas consisting of:    -   R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group        consisting of hydrido, methyl, ethyl, amidino, guanidino,        methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,        2-aminoethyl, N-methylamino, dimethylamino, methylthio,        ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl,        trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,        trifluoromethoxy, fluoro, chloro, amidosulfonyl,        N-methylamidosulfonyl, hydroxymethyl, carboxy, and cyano.

The compounds of this invention can be used in anticoagulant therapy forthe treatment and prevention of a variety of thrombotic conditionsincluding coronary artery and cerebrovascular disease. The compounds ofthis invention can be used to inhibit serine protease associated withthe coagulation cascade and factors II, VII, VIII, IX, X, XI, or XII.The compounds of the invention can inhibit the formation of bloodplatelet aggregates, inhibit the formation of fibrin, inhibit thrombusformation, and inhibiting embolus formation in a mammal, in blood, inblood products, and in mammalian organs. The compounds also can be usedfor treating or preventing unstable angina, refractory angina,myocardial infarction, transient ischemic attacks, atrial fibrillation,thrombotic stroke, embolic stroke, deep vein thrombosis, disseminatedintravascular coagulation, ocular build up of fibrin, and reocclusion orrestenosis of recanalized vessels in a mammal. The compounds can also beused in prophylactic treatment of subjects who are at risk of developingsuch disorders. The compounds can be used to lower the risk ofatherosclerosis. The compounds of Formula (I) would also be useful inprevention of cerebral vascular accident (CVA) or stroke.

Besides being useful for human treatment, these compounds are alsouseful for veterinary treatment of companion animals, exotic animals andfarm animals, including mammals, rodents, and the like. More preferredanimals include horses, dogs, and cats.

In yet another embodiment of the present invention, the novel compoundsare selected from the compounds set forth in Examples 1 through Example28 and Example Table 1.

The use of generic terms in the description of the compounds are hereindefined for clarity.

Standard single letter elemental symbols are used to represent specifictypes of atoms unless otherwise defined. The symbol “C” represents acarbon atom.

The symbol “O” represents an oxygen atom. The symbol “N” represents anitrogen atom. The symbol “P” represents a phosphorus atom. The symbol“S” represents a sulfur atom. The symbol “H” represents a hydrido atom.Double letter elemental symbols are used as defined for the elements ofthe periodical table (i.e., Cl represents chlorine, Se representsselenium, etc.).

As utilized herein, the term “alkyl”, either alone or within other termssuch as “haloalkyl” and “alkylthio”, means an acyclic alkyl radicalcontaining from 1 to about 10, preferably from 3 to about 8 carbon atomsand more preferably 3 to about 6 carbon atoms. Said alkyl radicals maybe optionally substituted with groups as defined below. Examples of suchradicals include methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl,oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl,tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl, octyl and the like.

The term “alkenyl” refers to an unsaturated, acyclic hydrocarbon radicalin so much as it contains at least one double bond. Such alkenylradicals contain from about 2 to about 10 carbon atoms, preferably fromabout 3 to about 8 carbon atoms and more preferably 3 to about 6 carbonatoms. Said alkenyl radicals may be optionally substituted with groupsas defined below. Examples of suitable alkenyl radicals includepropenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl,2-2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-yl,3-hydroxyhexen-1-yl, hepten-1-yl, and octen-1-yl, and the like.

The term “alkynyl” refers to an unsaturated, acyclic hydrocarbon radicalin so much as it contains one or more triple bonds, such radicalscontaining about 2 to about 10 carbon atoms, preferably having fromabout 3 to about 8 carbon atoms and more preferably having 3 to about 6carbon atoms. Said alkynyl radicals may be optionally substituted withgroups as defined below.

Examples of suitable alkynyl radicals include ethynyl, propynyl,hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl,4-methoxypentyn-2-yl, 3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl,hexyn-3-yl, 3,3-dimethylbutyn-l-yl radicals and the like.

The term “hydrido” denotes a single hydrogen atom (H). This hydridoradical may be attached, for example, to an oxygen atom to form a“hydroxyl” radical, one hydrido radical may be attached to a carbon atomto form a “methine” radical —CH═, or two hydrido radicals may beattached to a carbon atom to form a “methylene” (—CH₂—) radical.

The term “carbon” radical denotes a carbon atom without any covalentbonds and capable of forming four covalent bonds.

The term “cyano” radical denotes a carbon radical having three of fourcovalent bonds shared by a nitrogen atom.

The term “hydroxyalkyl” embraces radicals wherein any one or more of thealkyl carbon atoms is substituted with a hydroxyl as defined above.Specifically embraced are monohydroxyalkyl, dihydroxyalkyl andpolyhydroxyalkyl radicals.

The term “alkanoyl” embraces radicals wherein one or more of theterminal alkyl carbon atoms are substituted with one or more carbonylradicals as defined below. Specifically embraced are monocarbonylalkyland dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicalsinclude formyl, acetyl, and pentanoyl. Examples of dicarbonylalkylradicals include oxalyl, malonyl, and succinyl.

The term “alkylene” radical denotes linear or branched radicals havingfrom 1 to about 10 carbon atoms and having attachment points for two ormore covalent bonds. Examples of such radicals are methylene, ethylene,methylethylene, and isopropylidene.

The term “alkenylene” radical denotes linear or branched radicals havingfrom 2 to about 10 carbon atoms, at least one double bond, and havingattachment points for two or more covalent bonds. Examples of suchradicals are 1,1-vinylidene (CH₂═C), 1,2-vinylidene (—CH═CH—), and1,4-butadienyl (—CH═CH—CH═CH—).

The term “halo” means halogens such as fluorine, chlorine, bromine oriodine atoms.

The term “haloalkyl” embraces radicals wherein any one or more of thealkyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkylradicals. A monohaloalkyl radical, for one example, may have either abromo, chloro or a fluoro atom within the radical. Dihalo radicals mayhave two or more of the same halo atoms or a combination of differenthalo radicals and polyhaloalkyl radicals may have more than two of thesame halo atoms or a combination of different halo radicals. Morepreferred haloalkyl radicals are “lower haloalkyl” radicals having oneto about six carbon atoms. Examples of such haloalkyl radicals includefluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl,heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

The term “hydroxyhaloalkyl” embraces radicals wherein any one or more ofthe haloalkyl carbon atoms is substituted with hydroxy as defined above.Examples of “hydroxyhaloalkyl” radicals include hexafluorohydroxypropyl.

The term “haloalkylene radical” denotes alkylene radicals wherein anyone or more of the alkylene carbon atoms is substituted with halo asdefined above. Dihalo alkylene radicals may have two or more of the samehalo atoms or a combination of different halo radicals andpolyhaloalkylene radicals may have more than two of the same halo atomsor a combination of different halo radicals. More preferred haloalkyleneradicals are “lower haloalkylene” radicals having one to about sixcarbon atoms. Examples of “haloalkylene” radicals includedifluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkylsubstituted monofluoromethylene, and aryl substitutedtrifluoromethylene.

The term “haloalkenyl” denotes linear or branched radicals having from 1to about 10 carbon atoms and having one or more double bonds wherein anyone or more of the alkenyl carbon atoms is substituted with halo asdefined above. Dihaloalkenyl radicals may have two or more of the samehalo atoms or a combination of different halo radicals andpolyhaloalkenyl radicals may have more than two of the same halo atomsor a combination of different halo radicals.

The terms “alkoxy” and “alkoxyalkyl” embrace linear or branchedoxy-containing radicals each having alkyl portions of one to about tencarbon atoms, such as methoxy radical. The term “alkoxyalkyl” alsoembraces alkyl radicals having one or more alkoxy radicals attached tothe alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkylradicals. More preferred alkoxy radicals are “lower alkoxy” radicalshaving one to six carbon atoms. Examples of such radicals includemethoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyls. The“alkoxy” radicals may be further substituted with one or more haloatoms, such as fluoro, chloro or bromo, to provide “haloalkoxy” and“haloalkoxyalkyl” radicals. Examples of such haloalkoxy radicals includefluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy,trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, andfluoropropoxy. Examples of such haloalkoxyalkyl radicals includefluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl,difluoromethoxyethyl, and trifluoroethoxymethyl.

The terms “alkenyloxy” and “alkenyloxyalkyl” embrace linear or branchedoxy-containing radicals each having alkenyl portions of two to about tencarbon atoms, such as ethynyloxy or propenyloxy radical. The term“alkenyloxyalkyl” also embraces alkenyl radicals having one or morealkenyloxy radicals attached to the alkyl radical, that is, to formmonoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferredalkenyloxy radicals are “lower alkenyloxy” radicals having two to sixcarbon atoms. Examples of such radicals include ethynyloxy, propenyloxy,butenyloxy, and isopropenyloxy alkyls. The “alkenyloxy” radicals may befurther substituted with one or more halo atoms, such as fluoro, chloroor bromo, to provide “haloalkenyloxy” radicals. Examples of suchradicals include trifluoroethenyloxy, fluoroethenyloxy,difluoroethenyhloxy, and fluoropropenyloxy.

The term “haloalkoxyalkyl” also embraces alkyl radicals having one ormore haloalkoxy radicals attached to the alkyl radical, that is, to formmonohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term“haloalkenyloxy” also embraces oxygen radicals having one or morehaloalkenyloxy radicals attached to the oxygen radical, that is, to formmonohaloalkenyloxy and dihaloalkenyloxy radicals. The term“haloalkenyloxyalkyl” also embraces alkyl radicals having one or morehaloalkenyloxy radicals attached to the alkyl radical, that is, to formmonohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

The term “alkylenedioxy” radicals denotes alkylene radicals having atleast two oxygens bonded to a single alkylene group. Examples of“alkylenedioxy” radicals include methylenedioxy, ethylenedioxy,alkylsubstituted methylenedioxy, and arylsubstituted methylenedioxy. Theterm “haloalkylenedioxy” radicals denotes haloalkylene radicals havingat least two oxy groups bonded to a single haloalkyl group. Examples of“haloalkylenedioxy” radicals include difluoromethylenedioxy,tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstitutedmonofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy.

The term “aryl”, alone or in combination, means a carbocyclic aromaticsystem containing one, two or three rings wherein such rings may beattached together in a pendant manner or may be fused. The term “fused”means that a second ring is present (ie, attached or formed) by havingtwo adjacent atoms in common (ie, shared) with the first ring. The term“fused” is equivalent to the term “condensed”. The term “aryl” embracesaromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indaneand biphenyl.

The term “perhaloaryl” embraces aromatic radicals such as phenyl,naphthyl, tetrahydronaphthyl, indane and biphenyl wherein the arylradical is substituted with 3 or more halo radicals as defined below.

The term “heterocyclyl” embraces saturated and partially saturatedheteroatom-containing ring-shaped radicals having from 4 through 15 ringmembers, herein referred to as “C4C15 heterocyclyl” selected fromcarbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is aheteroatom. Heterocyclyl radicals may contain one, two or three ringswherein such rings may be attached in a pendant manner or may be fused.Examples of saturated heterocyclic radicals include saturated 3 to6-membered heteromonocylic group containing 1 to 4 nitrogen atoms [e.g.pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; saturated3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atomsand 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; saturated 3 to6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partiallysaturated heterocyclyl radicals include dihydrothiophene, dihydropyran,dihydrofuran and dihydrothiazole. Non-limiting examples of heterocyclicradicals include 2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl,1,3-dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4dioxanyl,morpholinyl, 1,4dithianyl, thiomorpholinyl, and the like.

The term “heteroaryl” embraces fully unsaturated heteroatom-containingring-shaped aromatic radicals having from 5 through 15 ring membersselected from carbon, nitrogen, sulfur and oxygen, wherein at least onering atom is a heteroatom. Heteroaryl radicals may contain one, two orthree rings wherein such rings may be attached in a pendant manner ormay be fused. Examples of “heteroaryl” radicals, include unsaturated 5to 6 membered heteromonocyclyl group containing 1 to 4 nitrogen atoms,for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl,3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl[e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.]tetrazolyl [e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturatedcondensed heterocyclic group containing 1 to 5 nitrogen atoms, forexample, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl,isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g.,tetrazolo [1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-memberedheteromonocyclic group containing an oxygen atom, for example, pyranyl,2-furyl, 3-furyl, etc.; unsaturated 5 to 6-membered heteromonocyclicgroup containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.;unsaturated 5- to 6-membered heteromonocyclic group containing 1 to 2oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl,isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic groupcontaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g.benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 5 to 6-memberedheteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g.,1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.;unsaturated condensed heterocyclic group containing 1 to 2 sulfur atomsand 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl,etc.] and the like. The term also embraces radicals where heterocyclicradicals are fused with aryl radicals. Examples of such fused bicyclicradicals include benzofuran, benzothiophene, and the like. Said“heterocyclyl” group may have 1 to 3 substituents as defined below.Preferred heterocyclic radicals include five to twelve membered fused orunfused radicals. Non-limiting examples of heteroaryl radicals includepyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl,pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl,furanyl, tetrazolyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl,pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl,1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyrazinyl, piperazinyl,1,3,5-triazinyl, 1,3,5-trithianyl, benzo(b)thiophenyl, benzimidazoyl,quinolinyl, tetraazolyl, and the like.

The term “sulfonyl”, whether used alone or linked to other terms such asalkylsulfonyl, denotes respectively divalent radicals —SO₂—.“Alkylsulfonyl”, embraces alkyl radicals attached to a sulfonyl radical,where alkyl is defined as above. “Alkylsulfonylalkyl”, embracesalkylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfonyl”, embraces haloalkyl radicalsattached to a sulfonyl radical, where haloalkyl is defined as above.“Haloalkylsulfonylalkyl”, embraces haloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above. The term“aminosulfonyl” denotes an amino radical attached to a sulfonyl radical.

The term “sulfinyl”, whether used alone or linked to other terms such asalkylsulfinyl, denotes respectively divalent radicals —S(O)—.“Alkylsulfinyl”, embraces alkyl radicals attached to a sulfinyl radical,where alkyl is defined as above. “Alkylsulfinylalkyl”, embracesalkylsulfinyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfinyl”, embraces haloalkyl radicalsattached to a sulfinyl radical, where haloalkyl is defined as above.“Haloalkylsulfinylalkyl”, embraces haloalkylsulfinyl radicals attachedto an alkyl radical, where alkyl is defined as above.

The term “aralkyl” embraces aryl-substituted alkyl radicals. Preferablearalkyl radicals are “lower aralkyl” radicals having aryl radicalsattached to alkyl radicals having one to six carbon atoms. Examples ofsuch radicals include benzyl, diphenylmethyl, triphenylmethyl,phenylethyl and diphenylethyl. The terms benzyl and phenylmethyl areinterchangeable.

The term “heteroaralkyl” embraces heteroaryl-substituted alkyl radicalswherein the heteroaralkyl radical may be additionally substituted withthree or more substituents as defined above for aralkyl radicals. Theterm “perhaloaralkyl” embraces aryl-substituted alkyl radicals whereinthe aralkyl radical is substituted with three or more halo radicals asdefined above.

The term “aralkylsulfinyl”, embraces aralkyl radicals attached to asulfinyl radical, where aralkyl is defined as above.“Aralkylsulfinylalkyl”, embraces aralkylsulfinyl radicals attached to analkyl radical, where alkyl is defined as above.

The term “aralkylsulfonyl”, embraces aralkyl radicals attached to asulfonyl radical, where aralkyl is defined as above.“Aralkylsulfonylalkyl”, embraces aralkylsulfonyl radicals attached to analkyl radical, where alkyl is defined as above.

The term “cycloalkyl” embraces radicals having three to 15 carbon atoms.More preferred cycloalkyl radicals are “lower cycloalkyl” radicalshaving three to seven carbon atoms. Examples include radicals such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Theterm cycloalkyl embraces radicals having seven to 15 carbon atoms andhaving two to four rings. Examples incude radicals such as norbornyl(i.e., bicyclo[2.2.1]heptyl) and adamantyl. The term “cycloalkylalkyl”embraces cycloalkyl-substituted alkyl radicals. Preferablecycloalkylalkyl radicals are “lower cycloalkylalkyl” radicals havingcycloalkyl radicals attached to alkyl radicals having one to six carbonatoms. Examples of such radicals include cyclohexylhexyl. The term“cycloalkenyl” embraces radicals having three to ten carbon atoms andone or more carbon-carbon double bonds. Preferred cycloalkenyl radicalsare “lower cycloalkenyl” radicals having three to seven carbon atoms.Examples include radicals such as cyclobutenyl, cyclopentenyl,cyclohexenyl and cycloheptenyl. The term “halocycloalkyl” embracesradicals wherein any one or more of the cycloalkyl carbon atoms issubstituted with halo as defined above. Specifically embraced aremonohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. Amonohalocycloalkyl radical, for one example, may have either a bromo,chloro or a fluoro atom within the radical. Dihalo radicals may have twoor more of the same halo atoms or a combination of different haloradicals and polyhalocycloalkyl radicals may have more than two of thesame halo atoms or a combination of different halo radicals. Morepreferred halocycloalkyl radicals are “lower halocycloalkyl” radicalshaving three to about eight carbon atoms. Examples of suchhalocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl,trifluorocyclopentyl, tetrafluorocyclohexyl, and dichlorocyclopropyl.The term “halocycloalkenyl” embraces radicals wherein any one or more ofthe cycloalkenyl carbon atoms is substituted with halo as defined above.

Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl andpolyhalocycloalkenyl radicals.

The term “cycloalkoxy” embraces cycloalkyl radicals attached to an oxyradical. Examples of such radicals includes cyclohexoxy andcyclopentoxy. The term “cycloalkoxyalkyl” also embraces alkyl radicalshaving one or more cycloalkoxy radicals attached to the alkyl radical,that is, to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals.Examples of such radicals include cyclohexoxyethyl. The “cycloalkoxy”radicals may be further substituted with one or more halo atoms, such asfluoro, chloro or bromo, to provide “halocycloalkoxy” and“halocycloalkoxyalkyl” radicals.

The term “cycloalkylalkoxy” embraces cycloalkyl radicals attached to analkoxy radical. Examples of such radicals includes cyclohexylmethoxy andcyclopentylmethoxy.

The term “cycloalkenyloxy” embraces cycloalkenyl radicals attached to anoxy radical. Examples of such radicals includes cyclohexenyloxy andcyclopentenyloxy. The term “cycloalkenyloxyalkyl” also embraces alkylradicals having one or more cycloalkenyloxy radicals attached to thealkyl radical, that is, to form monocycloalkenyloxyalkyl anddicycloalkenyloxyalkyl radicals. Examples of such radicals includecyclohexenyloxyethyl. The “cycloalkenyloxy” radicals may be furthersubstituted with one or more halo atoms, such as fluoro, chloro orbromo, to provide “halocycloalkenyloxy” and “halocycloalkenyloxyalkyl”radicals.

The term “cycloalkylenedioxy” radicals denotes cycloalkylene radicalshaving at least two oxygens bonded to a single cycloalkylene group.Examples of “alkylenedioxy” radicals include 1,2-dioxycyclohexylene.

The term “cycloalkylsulfinyl”, embraces cycloalkyl radicals attached toa sulfinyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfinylalkyl”, embraces cycloalkylsulfinyl radicals attachedto an alkyl radical, where alkyl is defined as above. The term“Cycloalkylsulfonyl”, embraces cycloalkyl radicals attached to asulfonyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfonylalkyl”, embraces cycloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above.

The term “cycloalkylalkanoyl” embraces radicals wherein one or more ofthe cycloalkyl carbon atoms are substituted with one or more carbonylradicals as defined below. Specifically embraced aremonocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples ofmonocarbonylcycloalkyl radicals include cyclohexylcarbonyl,cyclohexylacetyl, and cyclopentylcarbonyl. Examples ofdicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

The term “alkylthio” embraces radicals containing a linear or branchedalkyl radical, of one to ten carbon atoms, attached to a divalent sulfuratom. More preferred alkylthio radicals are “lower alkylthio” radicalshaving one to six carbon atoms. An example of “lower alkylthio” ismethylthio (CH₃—S—). The “alkylthio” radicals may be further substitutedwith one or more halo atoms, such as fluoro, chloro or bromo, to provide“haloalkylthio” radicals. Examples of such radicals includefluoromethylthio, chloromethylthio, trifluoromethylthio,difluoromethylthio, trifluoroethylthio, fluoroethylthio,tetrafluoroethylthio, pentafluoroethylthio, and fluoropropylthio.

The term “alkyl aryl amino” embraces radicals containing a linear orbranched alkyl radical, of one to ten carbon atoms, and one aryl radicalboth attached to an amino radical. Examples includeN-methyl-4-methoxyaniline, N-ethyl-4-methoxyaniline, andN-methyl-4-trifluoromethoxyaniline.

The terms alkylamino denotes “monoalkylamino” and “dialkylamino”containing one or two alkyl radicals, respectively, attached to an aminoradical.

The terms arylamino denotes “monoaryl amino” and “diarylamino”containing one or two aryl radicals, respectively, attached to an aminoradical. Examples of such radicals include N-phenylamino andN-naphthylamino.

The term “aralkylamino”, embraces aralkyl radicals attached to an aminoradical, where aralkyl is defined as above. The term aralkylaminodenotes “monoaralkylamino” and “diaralkylamino” containing one or twoaralkyl radicals, respectively, attached to an amino radical. The termaralkylamino further denotes “monoaralkyl monoalkylamino” containing onearalkyl radical and one alkyl radical attached to an amino radical.

The term “arylsulfinyl” embraces radicals containing an aryl radical, asdefined above, attached to a divalent S(O) atom. The term“arylsulfinylalkyl” denotes arylsulfinyl radicals attached to a linearor branched alkyl radical, of one to ten carbon atoms.

The term “arylsulfonyl”, embraces aryl radicals attached to a sulfonylradical, where aryl is defined as above. “arylsulfonylalkyl”, embracesarylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above. The term “heteroarylsulfinyl” embraces radicalscontaining an heteroaryl radical, as defined above, attached to adivalent S(O) atom. The term “heteroarylsulfinylalkyl” denotesheteroarylsulfinyl radicals attached to a linear or branched alkylradical, of one to ten carbon atoms. The term “Heteroarylsulfonyl”,embraces heteroaryl radicals attached to a sulfonyl radical, whereheteroaryl is defined as above. “Heteroarylsulfonylalkyl”, embracesheteroarylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above.

The term “aryloxy” embraces aryl radicals, as defined above, attached toan oxygen atom. Examples of such radicals include phenoxy,4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloroethylphenoxy,3,4-dichlorophenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy,3-trifluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy,5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy,4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy,3-isopropylphenoxy, 3-cyclopropylphenoxy, 3-ethylphenoxy,3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)-phenoxy, and4-tert -butylphenoxy.

The term “aroyl” embraces aryl radicals, as defined above, attached toan carbonyl radical as defined above. Examples of such radicals includebenzoyl and toluoyl.

The term “aralkanoyl” embraces aralkyl radicals, as defined herein,attached to an carbonyl radical as defined above. Examples of suchradicals include, for example, phenylacetyl.

The term “aralkoxy” embraces oxy-containing aralkyl radicals attachedthrough an oxygen atom to other radicals. More preferred aralkoxyradicals are “lower aralkoxy” radicals having phenyl radicals attachedto lower alkoxy radical as described above. Examples of such radicalsinclude benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethylbenzyloxy, 3,5-difluorobenyloxy, 3-bromobenzyloxy,4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, and2-phenylethoxy.

The term “aryloxyalkyl” embraces aryloxy radicals, as defined above,attached to an alkyl group. Examples of such radicals includephenoxymethyl.

The term “haloaryloxyalkyl” embraces aryloxyalkyl radicals, as definedabove, wherein one to five halo radicals are attached to an aryloxygroup.

The term “heteroaroyl” embraces heteroaryl radicals, as defined above,attached to an carbonyl radical as defined above. Examples of suchradicals include furoyl and nicotinyl.

The term “heteroaralkanoyl” embraces heteroaralkyl radicals, as definedherein, attached to an carbonyl radical as defined above. Examples ofsuch radicals include, for example, pyridylacetyl and furylbutyryl.

The term “heteroaralkoxy” embraces oxy-containing heteroaralkyl radicalsattached through an oxygen atom to other radicals. More preferredheteroaralkoxy radicals are “lower heteroaralkoxy” radicals havingheteroaryl radicals attached to lower alkoxy radical as described above.

The term “haloheteroaryloxyalkyl” embraces heteroaryloxyalkyl radicals,as defined above, wherein one to four halo radicals are attached to anheteroaryloxy group.

The term “heteroarylamino” embraces heterocyclyl radicals, as definedabove, attached to an amino group. Examples of such radicals includepyridylamino.

The term “heteroarylaminoalkyl” embraces heteroarylamino radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude pyridylmethylamino.

The term “heteroaryloxy” embraces heterocyclyl radicals, as definedabove, attached to an oxy group. Examples of such radicals include2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and4-pyridyloxy.

The term “heteroaryloxyalkyl” embraces heteroaryloxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude 2-pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl.

The term “arylthio” embraces aryl radicals, as defined above, attachedto an sulfur atom. Examples of such radicals include phenylthio.

The term “arylthioalkyl” embraces arylthio radicals, as defined above,attached to an alkyl group. Examples of such radicals includephenylthiomethyl.

The term “alkylthioalkyl” embraces alkylthio radicals, as defined above,attached to an alkyl group. Examples of such radicals includemethylthiomethyl. The term “alkoxyalkyl” embraces alkoxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude methoxymethyl.

The term “carbonyl” denotes a carbon radical having two of the fourcovalent bonds shared with an oxygen atom. The term “carboxy” embraces ahydroxyl radical, as defined above, attached to one of two unsharedbonds in a carbonyl group. The term “carboxamide” embraces amino,monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino,and dicycloalkylamino radicals, attached to one of two unshared bonds ina carbonyl group. The term “carboxamidoalkyl” embraces carboxamideradicals, as defined above, attached to an alkyl group. The term“carboxyalkyl” embraces a carboxy radical, as defined above, attached toan alkyl group. The term “carboalkoxy” embraces alkoxy radicals, asdefined above, attached to one of two unshared bonds in a carbonylgroup. The term “carboaralkoxy” embraces aralkoxy radicals, as definedabove, attached to one of two unshared bonds in a carbonyl group. Theterm “monocarboalkoxyalkyl” embraces one carboalkoxy radical, as definedabove, attached to an alkyl group. The term “dicarboalkoxyalkyl”embraces two carboalkoxy radicals, as defined above, attached to analkylene group. The term “monocyanoalkyl” embraces one cyano radical, asdefined above, attached to an alkyl group. The term “dicyanoalkylene”embraces two cyano radicals, as defined above, attached to an alkylgroup. The term “carboalkoxycyanoalkyl” embraces one cyano radical, asdefined above, attached to an carboalkoxyalkyl group.

The term “acyl”, alone or in combination, means a carbonyl orthionocarbonyl group bonded to a radical selected from, for example,hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl,haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy,arylthio, and alkylthioalkyl. Examples of “acyl” are formyl, acetyl,benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like.The term “haloalkanoyl” embraces one or more halo radicals, as definedherein, attached to an alkanoyl radical as defined above. Examples ofsuch radicals include, for example, chloroacetyl, trifluoroacetyl,bromopropanoyl, and heptafluorobutanoyl.

The term “phosphono” embraces a pentavalent phosphorus attached with twocovalent bonds to an oxygen radical. The term “dialkoxyphosphono”denotes two alkoxy radicals, as defined above, attached to a phosphonoradical with two covalent bonds. The term “diaralkoxyphosphono” denotestwo aralkoxy radicals, as defined above, attached to a phosphono radicalwith two covalent bonds. The term “dialkoxyphosphonoalkyl” denotesdialkoxyphosphono radicals, as defined above, attached to an alkylradical. The term “diaralkoxyphosphonoalkyl” denotes diaralkoxyphosphonoradicals, as defined above, attached to an alkyl radical.

The term “amino” denotes a nitrogen atom containing two substituentssuch as hydrido, hydroxy or alkyl and having one covalent bond availablefor bonding to a single atom such as carbon. Examples of such aminoradicals include, for example, —NH₂, —NHCH₃, —NHOH, and —NHOCH₃. Theterm “imino” denotes a nitrogen atom containing one substituent such ashydrido, hydroxy or alkyl and having two covalent bonds available forbonding to a single atom such as carbon. Examples of such imino radicalsinclude, for example, —NH, —NCH₃, —NOH, and —NOCH₃. The term “iminocarbonyl” denotes a carbon radical having two of the four covalent bondsites shared with an imino group. Examples of such imino carbonylradicals include, for example, C—NH, C—NCH₃, C—NOH, and C—NOCH₃. Theterm “amidino” embraces a substituted or unsubstituted amino groupbonded to one of two available bonds of an iminocarbonyl radical.Examples of such amidino radicals include, for example, NH₂—C—NH,NH₂—C—NCH₃, NH₂—C—NOCH₃ and CH₃NH—C—NOH. The term “guanidino” denotes anamidino group bonded to an amino group as defined above where said aminogroup can be bonded to a third group. Examples of such guanidinoradicals include, for example, NH₂—C(NH)—NH—, NH₂—C(NCH₃)—NH—,—NH₂—C(NOCH₃)—NH—, and CH₃NH—C(NOH)—NH—.

The term “sulfonium” denotes a positively charged trivalent sulfur atomwhere said sulfur is substituted with three carbon based groups such asalkyl, alkenyl, aralkyl, or aryl. The term “dialkyl sulfonium” denotes asulfonium group where said sulfur is substituted with two alkyl groups.Examples of such dialkylsulfonium radicals include, for example,(CH₃)₂S⁺—. The term “dialkyl sulfonium alkyl” denotes a dialkylsulfonium group where said group is bonded to one bond of an alkylenegroup as defined above. Examples of such dialkylsulfoniumalkyl radicalsinclude (CH₃)₂S⁺—CH₂CH₂—.

The term “phosphonium” denotes a positively charged tetravalentphosphorus atom where said phosphorus is substituted with four carbonbased groups such as alkyl, alkenyl, aralkyl, or aryl. The term“trialkyl phosphonium” denotes a phosphonium group where said phosphorusis substituted with three alkyl groups. Examples of suchtrialkylphosphonium radicals include, for example, (CH₃ )₃P⁺.

Said “alkyl”, “alkenyl”, “alkynyl”, “alkanoyl”, “alkylene”,“alkenylene”, “hydroxyalkyl”, “haloalkyl”, “haloalkylene”,“haloalkenyl”, “alkoxy”, “alkenyloxy”, “alkenyloxyalkyl”, “alkoxyalkyl”,“aryl”, “perhaloaryl”, “haloalkoxy”, “haloalkoxyalkyl”,“haloalkenyloxy”, “haloalkenyloxyalkyl”, “alkylenedioxy”,“haloalkylenedioxy”, “heterocyclyl”, “heteroaryl”, “hydroxyhaloalkyl”,“alkylsulfonyl”, “haloalkylsulfonyl”, “alkylsulfonylalkyl”,“haloalkylsulfonylalkyl”, “alkylsulfinyl”, “alkylsulfinylalkyl”,“haloalkylsulfinylalkyl”, “aralkyl”, “heteroaralkyl”, “perhaloaralkyl”,“aralkylsulfonyl”, “aralkylsulfonylalkyl”, “aralkylsulfinyl”,“aralkylsulfinylalkyl”, “cycloalkyl”, “cycloalkylalkanoyl”,“cycloalkylalkyl”, “cycloalkenyl”, “halocycloalkyl”, “halocycloalkenyl”,“cycloalkylsulfinyl”, “cycloalkylsulfinylalkyl”, “cycloalkylsulfonyl”,“cycloalkylsulfonylalkyl”, “cycloalkoxy”, “cycloalkoxyalkyl”,“cycloalkylalkoxy”, “cycloalkenyloxy”, “cycloalkenyloxyalkyl”,“cycloalkylenedioxy”, “halocycloalkoxy”, “halocycloalkoxyalkyl”,“halocycloalkenyloxy”, “halocycloalkenyloxyalkyl”, “alkylthio”,“haloalkylthio”, “alkylsulfinyl”, “amino”, “oxy”, “thio”, “alkylamino”,“arylamino”, “aralkylamino”, “arylsulfinyl”, “arylsulfinylalkyl”,“arylsulfonyl”, “arylsulfonylalkyl”, “heteroarylsulfinyl”,“heteroarylsulfinylalkyl”, “heteroarylsulfonyl”,“heteroarylsulfonylalkyl”, “heteroarylamiino”, “heteroarylaminoalkyl”,“heteroaryloxy”, “heteroaryloxylalkyl”, “aryloxy”, “aroyl”,“aralkanoyl”, “aralkoxy”, “aryloxyalkyl”, “haloaryloxyalkyl”,“heteroaroyl”, “heteroaralkanoyl”, “heteroaralkoxy”,“heteroaralkoxyalkyl”, “arylthio”, “arylthioalkyl”, “alkoxyalkyl”,“acyl”, “amidino”, “guanidino”, “dialkylsulfonium”,“trialkylphosphonium”, and “dialkylsulfoniumalkyl” groups defined abovemay optionally have 1 or more non-hydrido substituents such as amidino,guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy,heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy,cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl,cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl,halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio,nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino,aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy,alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl,cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lowercycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, arninoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido,carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl,diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

The term “spacer” can include a covalent bond and a linear moiety havinga backbone of 1 to 7 contiguous atoms. The spacer may have 1 to 7 atomsof a univalent or multi-valent chain. Univalent chains may beconstituted by a radical selected from ═C(H)—, ═C(R^(2a))—, —O—, —S—,—S(O)—, —S(O)₂—, —NH—, —N(R^(2a))—, —N═, —CH(OH)—, ═C(OH)—,—CH(OR^(2a))—, ═C(OR^(2a))—, and —C(O)— wherein R^(2a) is selected fromalkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl,alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl,haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl,heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, andheteroarylalkenyl. Multi-valent chains may consist of a straight chainof 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2or 3 or 4 or 5 or 6 atoms with a side chain. The chain may beconstituted of one or more radicals selected from: lower alkylene, loweralkenyl, —O—, —O—CH₂—, —S—CH₂—, —CH₂CH₂—, ethenyl, —CH═CH(OH)—, —OCH₂O—,—O(CH₂)₂O—, —NHCH₂—, —OCH(R^(2a))O—, —O(CH₂CHR^(2a))O—, —OCF₂O—,—O(CF₂)₂O—, —S—, —S(O)—, —S(O)₂—, —N(H)—, —N(H)O—, —N(R^(2a))O—,—N(R^(2a))—, —C(O)—, —C(O)NH—, —C(O)NR^(2a)—, —N═, —OCH₂—, —SCH₂—,S(O)CH₂—, —CH₂C(O)—, —CH(OH)-, =C(OH)-, —CH(OR^(2a))—, ═C(OR^(2a))—,S(O)₂CH₂—, and —NR^(2a)CH₂— and many other radicals defined above orgenerally known or ascertained by one of skill-in-the art. Side chainsmay include substituents such as 1 or more non-hydrido substituents suchas amidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl,aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl,halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl,cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl,heteroarylamnino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy,alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy,cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl,haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky,alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, lowercycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl,haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano,carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl.

Compounds of the present invention can exist in tautomeric, geometric orstereoisomeric forms. The present invention contemplates all suchcompounds, including cis- and trans-geometric isomers, E- andZ-geometric isomers, R— and S-enantiomers, diastereomers, d-isomers,1-isomers, the racemic mixtures thereof and other mixtures thereof, asfalling within the scope of the invention. Pharmaceutically acceptablesales of such tautomeric, geometric or stereoisomeric forms are alsoincluded within the invention.

The terms “cis” and “trans” denote a form of geometric isomerism inwhich two carbon atoms connected by a double bond will each have ahydrogen atom on the same side of the double bond (“cis”) or on oppositesides of the double bond (“trans”).

Some of the compounds described contain alkenyl groups, and are meant toinclude both cis and trans or “E” and “Z” geometric forms.

Some of the compounds described contain one or more stereocenters andare meant to include R, S, and mixtures of R and S forms for eachstereocenter present.

Some of the compounds described herein may contain one or more ketonicor aldehydic carbonyl groups or combinations thereof alone or as part ofa heterocyclic ring system. Such carbonyl groups may exist in part orprincipally in the “keto” form and in part or principally as one or more“enol” forms of each aldehyde and ketone group present. Compounds of thepresent invention having aldehydic or ketonic carbonyl groups are meantto include both “keto” and “enol” tautomeric forms.

Some of the compounds described herein may contain one or more amidecarbonyl groups or combinations thereof alone or as part of aheterocyclic ring system. Such carbonyl groups may exist in part orprincipally in the “keto” form and in part or principally as one or more“enol” forms of each amide group present. Compounds of the presentinvention having amidic carbonyl groups are meant to include both “keto”and “enol” tautomeric forms. Said amide carbonyl groups may be both oxo(C═O) and thiono (C═S) in type.

Some of the compounds described herein may contain one or more imine orenamine groups or combinations thereof. Such groups may exist in part orprincipally in the “imine” form and in part or principally as one ormore “enamine” forms of each group present. Compounds of the presentinvention having said imine or enamine groups are meant to include both“imine” and “enamine” tautomeric forms.

The present invention also comprises a treatment and prophylaxis inanticoagulant therapy for the treatment and prevention of a variety ofthrombotic conditions including coronary artery and cerebrovasculardisease in a subject, comprising administering to the subject havingsuch disorder a therapeutically-effective amount of a compound ofFormula (I):

or a pharmaceutically-acceptable salt thereof.

As a further embodiment, compounds of the present invention of Formula(I) or a pharmaceutically-acceptable salt thereof as defined above,comprise a treatment and prophylaxis of coronary artery disease,cerebrovascular disease and other coagulation cascade related disordersin a subject, comprising administering to the subject having suchdisorder a therapeutically-effective amount of compounds of formula (I)of the present invention or a pharmaceutically-acceptable salt thereof.

Compounds of the present invention of Formula (I) or apharmaceutically-acceptable salt thereof can also be used wheneverinhibition of blood coagulation is required such as to preventcoagulation of stored whole blood and to prevent coagulation in otherbiological samples for testing or storage. Thus coagulation inhibitorsof the present inhibition can be added to or contacted with stored wholeblood and any medium containing or suspected of containing plasmacoagulation factors and in which it is desired that blood coagulation beinhibited, e.g. when contacting the mammal's blood with materialselected from the group consisting of vascular grafts, stents,orthopedic prothesis, cardiac prosthesis, and extracorporeal circulationsystems.

Compounds of Formula (I) are capable of inhibiting activity of serineproteases related to the coagulation cascade, and thus could be used inthe manufacture of a medicament, a method for the prophylactic ortherapeutic treatment of diseases mediated by coagulation cascade serineproteases, such as inhibiting the formation of blood plateletaggregates, inhibiting the formation of fibrin, inhibiting thrombusformation, and inhibiting embolus formation in a mammal, in blood, inblood products, and in mammalian organs. The compounds also can be usedfor treating or preventing unstable angina, refractory angina,myocardial infarction, transient ischemic attacks, atrial fibrillation,thrombotic stroke, embolic stroke, deep vein thrombosis, disseminatedintravascular coagulation, ocular build up of fibrin, and reocclusion orrestenosis of recanalized vessels in a mammal. The compounds also can beused to study the mechanism of action of coagulation cascade serineproteases to enable the design of better inhibitors and development ofbetter assay methods. The compounds of Formula (I) would be also usefulin prevention of cerebral vascular accident (CVA) or stroke.

Also included in the family of compounds of Formula (I) are thepharmaceutically-acceptable salts thereof. The term“pharmaceutically-acceptable salt” embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula (I) may be prepared frominorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, examples of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic,aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic,p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic,cyclohexylaminosulfonic, algenic, galacturonic acid. Suitablepharmaceutically-acceptable base addition salts of compounds of Formula(I) include metallic salts made from aluminum, calcium, lithium,magnesium, potassium, sodium and zinc or organic salts made fromN,N′-dibenzylethyleneldiamine, choline, chloroprocaine, diethanolamine,ethylenediaamine, meglumine (N-methylglucamine) and procain. All ofthese salts may be prepared by conventional means from the correspondingcompound of Formula (I) by reacting, for example, the appropriate acidor base with the compound of Formula (I).

The present invention also comprises a pharmaceutical compositioncomprising a therapeutically-effective amount of a compound of Formulas(I) in association with at least one pharmaceutically-acceptablecarrier, adjuvant or diluent. Pharmaceutical compositions of the presentinvention can comprise the active compounds of Formula (I) inassociation with one or more non-toxic, pharmaceutically-acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as “carrier” materials) and, if desired, other activeingredients. The active compounds of the present invention may beadministered by any suitable route, preferably in the form of apharmaceutical composition adapted to such a route, and in a doseeffective for the treatment intended.

The active compounds and composition may, for example, be administeredorally, intravascularly, intraperitoneally, subcutaneously,intramuscularly, oculary, or topically. For treating ocular build up offibrin, the compounds may be administered intraocularly or topically aswell as orally or parenterally.

The compounds can be administered in the form of a depot injection orimplant preparation which may be formulated in such a manner as topermit a sustained release of the active ingredient. The activeingredient can be compressed into pellets or small cylinders andimplanted subcutaneously or intramusculary as depot injections orimplants. Implants may employ inert materials such as biodegradablepolymers or synthetic silicones, for example, Silastic, silicone rubberor other silicon containing polymers.

The compounds can also be administered in the form of liposome deliverysystems, such as small unilamellar vesicles, large unilamellar vesiclesand multilamellar vesicles. Liposomes can be formed from a variety ofphospholipids, such as cholesterol, stearylamine orphospbatidylcholines.

The compounds may also be delivered by the use of monoclonal antibodiesas individual carriers to which the compound molecules are coupled. Thecompounds may also be coupled with soluble polymers as targetable drugcarriers. Such polymers can include polyvinylpyrrolidone, pyrancopolymer, polyhydroxy-propyl-methacrylamide-phenol,polyhydroxyethyl-aspartamide-phenol, or ployethyleneoxide-polylysinesubstituted with palmitoyl residues. Furthermore, the compounds may becoupled to a class of biodegradable polymers useful in achievingcontrolled release of a drug, for example, polylactic acid, polyglycolicacid, copolymers of polylactic and polyglycolic acid, polyepsiloncaprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals,polydihydropyrans, polycyanoacrylates and cross linked or amphitpathicblock copolymers of hydrogels.

For oral administration, the pharmaceutical composition may be in theform of, for example, tablets, capsules (each of which includessustained release or timed release formulations), pills, powders,granules, elixers, tinctures, suspensions, liquids including syrups, andemulsions. The pharmaceutical composition is preferably made in the formof a dosage unit containing a particular amount of the activeingredient. Examples of such dosage units are tablets or capsules. Theactive ingredient may also be administered by injection as a compositionwherein, for example, saline, dextrose or water may be used as asuitable carrier.

The amount of therapeutically active compounds which are administeredand the dosage regimen for treating a disease condition with thecompounds and/or compositions of this invention depends on a variety offactors, including the age, weight, sex and medical condition of thesubject, the severity of the disease, the route and frequency ofadministration, and the particular compound employed, and thus may varywidely.

The pharmaceutical compositions may contain active ingredients in therange of about 0.1 to 2000 mg, and preferably in the range of about 0.5to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, andpreferably between about 0.5 and about 20 mg/kg body weight, may beappropriate. The daily dose can be administered in one to four doses perday.

The compounds may be formulated in topical ointment or cream, or as asuppository, containing the active ingredients in a total amount of, forexample, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably0.4 to 15% w/w. When formulated in an ointment, the active ingredientsmay be employed with either paraffinic or a water-miscible ointmentbase.

Alternatively, the active ingredients may be formulated in a cream withan oil-in-water cream base. If desired, the aqueous phase of the creambase may include, for example at least 30% w/w of a polyhydric alcoholsuch as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol,polyethylene glycol and mixtures thereof. The topical formulation maydesirably include a compound which enhances absorption or penetration ofthe active ingredient through the skin or other affected areas. Examplesof such dermal penetration enhancers include dimethylsulfoxide andrelated analogs. The compounds of this invention can also beadministered by a transdermal device. Preferably topical administrationwill be accomplished using a patch either of the reservoir and porousmembrane type or of a solid matrix variety. In either case, the activeagent is delivered continuously from the reservoir or microcapsulesthrough a membrane into the active agent permeable adhesive, which is incontact with the skin or mucosa of the recipient. If the active agent isabsorbed through the skin, a controlled and predetermined flow of theactive agent is administered to the recipient. In the case ofmicrocapsules, the encapsulating agent may also function as themembrane.

The oily phase of the emulsions of this invention may be constitutedfrom known ingredients in a known manner. While the phase may comprisemerely an emulsifier, it may comprise a mixture of at least oneemulsifier with a fat or an oil or with both a fat and an oil.Preferably, a hydrophilic emulsifier is included together with alipophilic emulsifier which acts as a stabilizer. It is also preferredto include both an oil and a fat. Together, the emulsifier(s) with orwithout stabilizer(s) make-up the so-called emulsifying wax, and the waxtogether with the oil and fat make up the so-called emulsifying ointmentbase which forms the oily dispersed phase of the cream formulations.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the present invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate,among others.

The choice of suitable oils or fats for the formulation is based onachieving the desired cosmetic properties, since the solubility of theactive compound in most oils likely to be used in pharmaceuticalemulsion formulations is very low. Thus, the cream should preferably bea non-greasy, non-staining and washable product with suitableconsistency to avoid leakage from tubes or other containers. Straight orbranched chain, mono- or dibasic alkyl esters such as diisoadipate,isocetyl stearate, propylene glycol diester of coconut fatty acids,isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate,2-ethylhexyl palmitate or a blend of branched chain esters may be used.These may be used alone or in combination depending on the propertiesrequired. Alternatively, high melting point lipids such as white softparaffin and/or liquid paraffin or other mineral oils can be used.

For therapeutic purposes, the active compounds of the present inventionare ordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered per os, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, and/or various buffers. Other adjuvants and modes ofadministration are well and widely known in the pharmaceutical art.

In practicing the methods of the present invention for the treatment andprevention of a variety of thrombotic conditions including coronaryartery and cerebrovascular disease, the compounds and pharmaceuticalcompositions of the present invention are administered alone or incombination with one another, or in combination with other therapeuticsor in vivo diagnostic agents. The coagulation cascade inhibitors of thepresent invention can also be co-administered with suitableanti-platelet agreggation agents, including, but not limited toticlopidine or clopidrogel, fibrinogen receptor antagonists (e.g. totreat or prevent unstable angina or to prevent reocculsion afterangioplasty and restenosis), anti-coagulants such as aspirin, warfarinor heparins, thrombolytic agents such as plasminogen activators orstreptokinase to achieve synergistic effects in the treatment of variouspathologies, lipid lowering agents including antihypercholesterolemics(e.g. HMG CoA reductase inhibitors such as mevastatin, lovastatin,simvastatin, pravastatin, and fluvastatin, HMG CoA synthataseinhibitors, etc.), anti-diabetic drugs, or other cardiovascular agents(loop diuretics, thiazide type diuretics, nitrates, aldosteroneantagonistics (i.e., spironolactone and epoxymexlerenone), angiotensinconverting enzyme (e.g. ACE) inhibitors, angiotensin II receptorantagonists, beta-blockers, antiarrythmics, anti-hypertension agents,and calcium channel blockers) to treat or prevent atheriosclerosis. Forexample, patients suffering from coronary artery disease, and patientssubjected to angioplasty procedures, would benefit from coadministrationof fibrinogen receptor antagonists and coagulation cascade inhibitors ofthe present invention. Also, coagulation cascade inhibitors couldenhance the efficiency of tissue plasminogen activator-mediatedthrombolytic reperfusion.

Typical doses of coagulation cascade inhibitors of the present inventionwith other suitable anti-platelet agents, anticoagulation agents,cardiovascular therapeutic agents, or thrombolytic agents may be thesame as those doses of coagulation cascade inhibitors administeredwithout coadministration of additional anti-platelet agents,anticoagulation agents, cardiovascular therapeutic agents, orthrombolytic agents, or may be substantially less than those doses ofcoagulation cascade inhibitors administered without coadministration ofadditional anti-platelet agents, anticoagulation agents, cardiovasculartherapeutic agents, or thrombolytic agents, depending on a patient'stherapeutic needs.

All mentioned references are incorporated by reference as if herewritten.

Although this invention has been described with respect to specificembodiments, the details of these embodiments are not to be construed aslimitations. The following examples are provided to illustrate thepresent invention and are not intended to limit the scope thereof.Without further elaboration, it is believed that one skilled in the artcan, using the preceding descriptions, utilize the present invention toits fullest extent. Therefore the following preferred specificembodiments are to be construed as merely illustrative and notlimitative of the remainder of the disclosure in any way whatsoever.Compounds containing multiple variations of the structural modificationsillustrated in the schemes or the following Examples are alsocontemplated. Those skilled in the art will readily understand thatknown variations of the conditions and processes of the followingpreparative procedures can be used to prepare these compounds.

One skilled in the art may use these generic methods to prepare thefollowing specific examples, which have been or may be properlycharacterized by ¹H NMR, mass spectrometry, elemental composition, andsimilar procedures. These compounds also may be formed in vivo.

The following examples contain detailed descriptions of the methods ofpreparation of compounds of Formula (I). These detailed descriptionsfall within the scope and are presented for illustrative purposes onlyand are not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are Degrees centigrade unlessotherwise indicated.

The following general synthetic sequences are useful in making thepresent invention. Abbreviations used in the schemes and tables include:“AA” represents amino acids, “AcCN” represents acetonitrile, “AcOH”represents acetic. acid, “BINAP” represents2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, “BnOH” represents benzylalcohol, “BnCHO” represents 2-phenylethanal,“BnSO₂Cl” representsbenzylsulfonyl chloride, “Boc” represents tert-butyloxycarbonyl, “BOP”represents benzotriazol-1-yl-oxy-tris-(dimethylamino), “bu” representsbutyl, “dba” represents dibenzylidene-acetone, “DCC” represents1,3-dicyclohexylcarbodiimide, “DCM” represents dichloromethane ormethylene chloride, “DIBAH” or “DIBAL” represents diisobutylaluminumhydride, “DMF” represents dimethylformamide, “DMSO” representsdimethylsulfoxide, “DPPA” represents diphenylphosphoryl azide”, “EDC”represents 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride, “Ex. No.” represents Example Number, “Fmoc” represents9-fluorenylmethoxycarbonyl, “HOBt” represents hydroxybenzoltriazole,“LDA” represents lithium diisopropylamide, “MW” represents molecularweight, “NMM” represents N-methylmorpholine, “Ph” represents phenyl oraryl, “PHTH” represents a phthaloyl group, “pnZ” represents4nitrobenzyloxy-carbonyl, “PTC” represents a phase transfer catalyst,“py” represents pyridine, “RNH₂” represents a primary organic amine,“SEM” represents 2-(trimethylsilyl)ethoxy-methyl chloride, “p-TsOH”represents paratoluenesulfonic acid, “TBAF” representstetrabutylammonium fluoride, “TBTU” represents2-(1H-benzotriozole-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborate,“TEA” represents triethylamine, “TFA” represents trifluoroacetic acid,“THF” represents tetrahydrofuran, “TMS” represents trimethylsilyl,“TMSCN” represents trimethylsilyl cyanide, and “Cbz” or “Z” representsbenzyloxycarbonyl.

GENERAL SYNTHETIC PROCEDURES AND SPECIFIC EXAMPLES

The pyridone compounds of the present invention can be synthesized, forexample, according to the following procedures and Schemes given below.

A pyridone having a fused aryl or heteroaryl group can be considered tobe a quinolone. A generic quinolinone analogous structure to the basicpyridone ring type is shown in FIG. 1. W, X, Y and Z are optionallyselected from CH,

N, CF, CCl, C—CN, C—CH₃, C—CH₂CH₃, C—NH₂, C—CH₂NH₂, C—CH₂NHCH₃, C—NHCH₃,C—N(CH₃)₂, C—CH(NH₂)CH₃, C—CH₂CH₂NH₂, C—NHOCH₃, C—NHOCH₂CH₃, C—C(NH)NH₂,C—C(NOH)NH₂, C—OH, C—CH₂OH, C—CH₂CH₂OH, C—CH(OH)CH₃, C—OCH₃, C—OCH₂CH₃,C—CO₂H, C—CO₂CH₃, C—C(O)NH₂, C—C(O)NHCH₃, C—C(O)NH(CH₃)₂, C—CH₂CO₂H,C—SO₂NH₂, C—SO₂NHCH₃, C—NH(O)CCH₃, and C—NH(O)CCF₃. Quinolones in whichW of W—X═Y-Z is attached to the four and five positions of the pyridoneinstead of the five and six positions can be prepared by comparableprocedures. A general procedure for the preparation a wide variety ofquinolone type 2-pyridones is summarized in Scheme 1 and Scheme 2. Theseprocedures can accommodate the introduction of a wide range ofsubstituents into the fused ring either as such, precursors groups fordesired groups (for example, a nitro for subsequent conversion to anamino, an acetoxymethyl for subsequent hydrolysis to an hydroxymethyl oroxidation to an aldehyde or carboxylic acid, and the like) or usingprotected groups. The preparation of specific quinolinone analogues of apyridone of this invention are exemplified as in Example 1 throughExample 16.

Example 1

EX-1A) 3-Nitro-1H-Quinolin-2-One (2.35 g, 12.37 mmole) in 50 mlanhydrous DMF was mixed with NaH 60% in mineral oil (0.59 g, 14.87 g),and the mixture was stirred for five minutes. To this mixture,2-methyl-2-bromoacetate (2.27 g, 14.84 mmole) was added dropwise. Afterstirring the reaction mixture for 2 hours at 20° C., DMF was removed viavacuum rotary evaporation to lead to a yellow oil residue. The residuewas triturated in water to yield a yellow solid that was washed withwater and hexane. The yellow solid was re-crystallized in ethylacetateto yield a yellow needle crystal solid (1.38 g) as the expected product,methyl-(3-nitro-2-oxo-2H-quinolin-1-yl)acetate. More product (1.20 g)was obtained from the mother liquor via silica gel flash chromatographyto separate it from the O-alkylated side product (0.334 g). The desiredproduct (EX-1A) yield was 80%. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min@ 254 nm @ 50° C.): retention time 2.48 min, M+H⁺=263.2 for formulaC₁₂H₁₀N₂O₅. ¹H NMR (400 MHz, CDCl₃): δ 3.80 (s, 3H), 5.17 (s, 2H), 7.19(d, J=8.4 Hz, 1H), 7.40 (t, J=7.6 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 7.78(d, J=8.4 Hz, 1H), 8.61 (s, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 44.2, 52.9,114.2, 111.1, 124.0, 131.7, 134.8, 137.9, 140.6, 154.0, 167.6.

EX-1B) Compound EX-1A (2.51 g, 9.58 mmole) was mixed with 10% Pd onactivated carbon (0.51 g, 0.48 mmole) in 150 ml methanol. The mixturewas stirred under H₂ that was introduced through a rubber balloon for 2hours. The reaction mixture was filtered, and the methanol was removedto yield a white crystalline solid (2.06 g, y=93%) asmethyl-(3-amino-2-oxo-2H-quinolin-1-yl)acetate (3). HPLC-MS (0 to 95%AcCN/6 min @ 1.0 mL/Mn @ 254 nm @ 50° C.): retention time 2.12 min,M+H⁺=233.1 for formula C₁₂H₁₂N₂O₃. Compound 3 (2.04 g, 8.79 mmole) andpyridine (3.55 ml, 43.95 mmole) were dissolved in 200 ml acetonitrile.This mixture was cooled down to −1020 C. with a water-acetone-dry icemixture bath. To this mixture, a-tolunesulfonyl chloride (4.19 g, 21.98mmole) dissolved in 10 ml acetonitrile was added dropwise quickly. Thereaction mixture was stirred for 2.5 hours from −10° C. to 0° C. Duringthe reaction, the product as a white solid precipitated from thesolution. The pure product,methyl-(3-benzylsulfonylamido-2-oxo-2H-quinolin-1-yl)acetate (EX-1B)(2.92 g) was obtained by filtration and washing it with acetonitrile.More product (0.34 g) was obtained by working up the filtrate andsubjecting it to a Biotage-40 silica gel column chromatography using 25%ethylacetate in hexane as the elute. HPLC-MS (0 to 95% AcCN/6 min @ 1.0mL/Min @ 254 nm @ 50° C.): retention time 3.52 min, M+Na⁺=408.9 forformula C₁₉H₁₈N₂O₅SNa. ¹H NMR (400 MHz, CDCl₃): δ 3.81 (s, 3H), 4.42 (s,2H), 5.14 (s, 2H), 7.09 (d, J=8.8 Hz, 1H), 7.27 (m, 5H), 7.48 (t, J=7.6Hz, 2H), 7.61 (d, J=10 Hz, 1H), 8.61 (s, 1H). ¹³C NMR (101 MHz, CDCl₃):δ 44.5, 52.8, 58.5, 113.3, 119.5, 120.4, 123.5, 127.2, 127.8, 128.7,128.8, 129.0, 129.2, 130.8, 135.2, 157.3, 167.9.

EX-1C) Compound EX-1B (3.19 g,8.26 mmole) was dissolved in 50 ml THF, 30ml MeOH and 50 ml 1 M LiOH. The mixture was stirred at 20° C. for onehour. The mixture was concentrated to remove the organic solvents. Theremaining aqueous solution was acidified to pH=1 with 1M HCl, and asolid precipitated from the solution. The solid was purified byfiltration, washing with 1M HCl and water, and drying via vacuum to givea white solid as the pure product(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetic acid (EX-1C) (2.98g, yield of 97%). HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @50° C.): retention time 3.09 min, M+Na⁺=395.2 for forrnulaC₁₈H₁₆N₂O₅SNa. ¹H NMR (400 MHz, CDCl₃): δ 4.54 (s, 2H), 5.13 (s, 2H),7.15 (t, J=87.2 Hz, 1H), 7.23 (m, 3H), 7.33 (m, 3H), 7.50 (t, J=7.6 Hz,2H), 7.59 (s, 1H).

EX-1D) Compound EX-1C (0.209 g, 0.56 mmol), EDC (0.140 g, 0.73 mmol) andHOBt (0.112 g, 0.73 mmol) were mixed in 1.5 ml DMF, and the mixture wasstirred at 20° C. for 10 minutes. To this mixture was added the premixedsolution of(4S)-(9Cl)-N-[[[4-amino-5-hydroxy-5-(2-thiazolyl)pentyl]amino]iminomethyl]-4-methoxy-2,3,6-trimethylbenzenesulfonamideHCl salt (0.387 g, 0.73 mmol), diisopropylethylamine (0.65 ml, 3.93mmol) in 1.5 ml DMF. The combined reaction mixture was stirred for 45minutes at 20° C. The reaction mixture was partitioned betweenethylacetate and saturated ammonium chloride aqueous solution. Theorganic phase was washed with saturated aqueous potassium carbonate andammonium chloride solution, dried over Na₂SO₄ After removing theethylacetate, the residue was subjected to a Biotage silica gel columnchromatography to yield a white solid as the productN-[2(S)-1(R,S)-2-[1-hydroxy-1-(2-thiazolyl)]-5-[[(4-methoxy-2,3,6-trimethyl)sulfonylamino]-iminomethyl]aminopentyl]-[3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamide(EX-1D) (0.347 g, y=76%). HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @254 nm @ 50° C.): retention time 3.75 min, M+H⁺=810.3 for formulaC₃₇H₄₃N₇O₈S₃. Since the compound is a mixture of two diastereomers, the¹H NMR and ¹³C NMR was complex.

EX-1E) Compound EX-1D (0.32 g, 0.395 mmol) was mixed with1,3-dihydro-1-hydroxy-3,3-bis(trifluoromethyl)-1-oxide-1,2-benziodoxole(0.238 g, 0.593 mmole) in 5 ml acetonitrile. The mixture was stirred at20° C. for 2 hours. It was then mixed with 30 ml 1M NaHSO₃ aqueoussolution. The combined solution was extracted with ethylacetate, and theorganic phase was washed with saturated NaHCO₃ aqueous solution anddried over Na₂SO₄. After removing the ethylacetate, the remainingresidue was subjected to a silica gel flash column chromatography using30% ethylacetate in hexane as elute to yield a white solid as theproductN-[[2(S)-2-[1-Oxo-1-(2-thiazolyl)]-5-[[[(4-methoxy-2,3,6-trimethyl)sulfonylanoliminomethyl]amino]pentyl]-(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamide(EX-1E) (0.296 g, 93%). HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254nm @ 50° C.): retention time 4.07 min, M+H⁺=808.2 for formulaC₃₇H₄₁N₇O₈S₃. ¹H NMR (400 MHz, acetone-d₆): δ 1.71 (b, 4H), 2.07 (s,3H), 2.59 (s, 3H), 2.64 (s, 3H), 3.24 (m, 2H), 3.80 (s, 3H), 4.62 (s,2H), 5.17 (d, J=−16.4 Hz, 1H), 5.22(d, J=16.4Hz, 1H), 5.62 (m, 1H), 6.47(b, 2H), 6.64(s, 1H), 7.24 (m, 4H), 7.36 (m, 3H), 7.44 (m, 2H), 7.59 (t,J=7.2 Hz, 2H), 7.95 (b, 1H), 8.08 (m, 3H). ¹³C NMR (101 MHz, CDCl₃): δ12.0, 15.6, 18.6, 24.2, 41.1, 46.6, 55.8, 55.9, 58.5, 66.1, 112.3,120.3, 121.2, 123.8, 124.8, 128.5, 129.1, 129.2, 129.3, 129.6, 129.7,129.9, 123.0, 131.9, 135.8, 136.7, 137.0, 139.0, 146.1, 157.4, 158.0,158.8, 165.6, 167.7, 192.0.

Compound EX-1E (0.240 g, 0.296 mmol) was treated with thioanisole (0.220g, 1.78 mmol) and 8 ml trifluoroacetic acid for 5 hours. After removingthe TFA, the residue was triturated in diethylether twice andethylacetate once to give a white amorphous solid as the productN-[[2(S)-2-[1-Oxo-1-(2-thiazolyl)]-5-[(amino)iminomethyl)amino]pentyl]-(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamidetrifluoroacetic acid salt (0.183 g, yield of 87%). HPLC-MS (0 to 95%AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time 3.07 min,M+H⁺=596.2 for formula C₂₇H₂₉N₇O₅S₂. ¹H NMR (400 MHz, DMSO-d₆): δ 1.58(bm, 2H), 1.67 (bm, 1H), 1.90 (b, 1H), 3.10 (bm, 2H), 4.60 (s, 2H), 3.80(s, 3H), 4.62,(s, 2H), 5.01 (d, J=−17.2 Hz, 1H), 5.11 (d, J=−17.2 Hz,1H), 5.38 (m, 1H), 6.80-7.70 (m, 15H), 8.14(s, 1H), 8.23 (s, 1H), 8.88(b, 1H), 9.99 (d, J=8.0 Hz, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ 25.3,28.0, 44.9, 48.6, 54.4, 58.0, 114.2, 119.7, 121.9, 124.8,.126.1, 128.2,128.3, 128.7, 131.0, 135.9, 137.1, 138.7, 144.7, 145.4, 156.6, 157.4,164.4, 166.8, 191.4.

Example 2

EX-2A) 3-Benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetic acid wascoupled with benzyl-[[(4-aminomethylphenyl)iminomethyl]amino]carbamatehydrogen chloride salt using EDC, HOBt as coupling agents in thepresence of DIEA in DMF. Work up procedure gave a white amorphous solidas the product,N-[[4-[(benzylcarbonyl-amino)iminomethyl]phenyl]methyl]-(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamide.HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retentiontime 3.38 min, M+H⁺=638.3 for formula C₃₄H₃₁N₅O₆S. ¹H NMR (400 MHz,CDCl₃): δ 4.38 (s, 2H), 4.50 (d, J=6.0Hz, 2H), 4.92 (s, 2H), 5.14 (s,2H), 7.06 (t, J=7.2 Hz, 1H), 7.13 (t, J=7.6 Hz, 2H), 7.15-7.24 (m, 6H),7.30-7.40 (m, 6H), 7.45 (m, 3H), 7.52 (m, 1H), 7.57 (d, J=8.4 Hz, 2H),8.65(b, 1H), 9.09 (b, 1H).

Compound EX-2A (0.118 g, 0.185 mmol),p-toluenesulfonic acid mono hydrate(0.035 g, 0.185 mmol) and 10% Pd on activated carbon (0.029 g, 0.018mmol) were mixed with 5 ml methanol. The mixture was stirred for 2 hoursunder an atmosphere of hydrogen that was introduced through a rubberballoon. After filtering off the catalyst and removing the methanol, theremaining residue was recrystallized in a solvent of 2:1 ether tomethanol to yield a white amorphous solid as the product,N-[[4-[(amino)iminomethyl]phenyl]methyl]-(3-benzylsulfonyl-amino-2-oxo-2H-quinolin-1-yl)acetamidep-toluenesulfonic acid salt, (0.080 g, yield=64%). HPLC-MS (0 to 95%AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time 2.81 min,M+H⁺=504.5 for formula C₂₆H₂₅N₅O₄S. ¹H NMR (400 MHz, CD₃OD): δ 2.36 (s,3H), 4.52 (s, 2H), 4.57 (s, 2H), 5.15 (s, 2H), 7.18-7.32 (m, 7H), 7.36(t, J=7.2 Hz, 2H), 7.48-7.55 (m, 4H), 7.59 (s, 1H), 7.70 (d, J=8.0 Hz,2H), 7.74 (d, J=8.4 Hz, 2H).

Example 3

EX-3A) Methyl 2-[3-amino-2-oxo-2H-quinolin-1-yl]acetate, (9.1 g, 39.2mmol) was mixed with Boc anhydride (9.41 g, 43.1 mmol), triethylamine (6ml, 43.1 mmol) and DMAP (50 mg, 0.4 mmol) in 200 ml DCM. The reactionmixture was stirred at 20° C. for 14 hours. The reaction solution waswashed with 1M citric acid solution twice, saturated sodium bicarbonatesolution three times, saturated ammonium chloride once and it was driedover anhydrous MgSO₄. After filtration and removing the solvent, theresidue was treated with methanol. A white solid was precipitated.Filtration and washing with methanol, the pure product, EX-3A, wasobtained as a white powder (9.90 g, 87%). HPLC-MS (0 to 95% AcCN/6 min @1.0 mL/Min @ 254 nm @ 50° C.): retention time 2.85 min, M+H⁺=291.1 forformula C₁₄H₁₅N₂O₅. ¹H NMR (400 MHz, Methanol-d₄): d 3.76 (s, 3H), 3.82(s, 3H), 5.15 (s, 2H), 7.09 (d, J=8.4 Hz, 1H), 7.26 (t, J=7.6Hz, 1H),7.43 (t, J=7.6 Hz, 2H), 7.61 (d, J=7.6 Hz, 1H), 7.96 (s, 1H), 8.39 (s,1H). ¹³C NMR (101 MHz, Methanol-d₄): d (ppm) 44.4, 52.5, 52.6, 113.1,118.9, 121.0, 123.3, 127.4, 128.4, 128.5, 134.5, 153.9, 157.6, 168.1.

EX-3B) Compound EX-3A (1.09 g, 3.75 mmol) was mixed with KOH (5.2 , 92.8mmol) in 30 ml water and 30 ml methanol. After refluxing for threehours, the reaction solution was concentrated to 10 ml and acidifiedwith concentrated HCl to pH=2. After cooling down to 0° C., the productwas filtered out, washed with water and dried via vacuum. A yellowpowder acid was obtained as the pure product (0.733 g, y=90%). HPLC-MS(0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time1.60 min, M+H⁺=219.1 for formula C₁₁H₁₁N₂O₃.

EX-3C) Compound EX-3B (0.296 g, 1.16 mmol) was treated withphenylacetaldehyde (0.21 g, 1.74 mmol) in 15 ml methanol for 10 minutes.To this mixture was added sodium cyanoborohydride (0.08 g,1.28 mmol).After two hours, the reaction was completed. Methanol was removed underreduced pressure and the residue was mixed with water. The product2-[3-(2-phenylethylamino)-2-oxo-2H-quinolin-1-yl]acetic acid (EX-3C) wasobtained after filtration and washed with water as a white powder (0.225g, 60%). HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.):retention time 3.55 min, M+H⁺=323.2 for formula C₁₉H₁₉N₂O₃. ¹H NMR (400MHz, Methanol-d₄): d 2.97 (t, J=7.2 Hz, 2H), 3.45 (t, J=7.2 Hz, 2H),5.02 (s, 2H), 6.65 (s, 1H), 7.13-7.29 (m, 8H), 7.46 (d, J=8.0Hz, 1H).¹³C NMR (101 MHz, Methanol-d₄): d (ppm) 35.9, 45.5, 46.6, 105.7, 115.1,123.9, 124.5, 125.9, 127.0, 127.4, 129.6, 129.8, 133.9, 137.8, 140.8,159.9, 173.1.

EX-3D) Compound EX-3D was synthesized in same way as described forcompound EX-2A. It is a white powder. HPLC-MS (0 to 95% AcCN/6 min @ 1.0mL/Min @ 254 nm @ 50° C.): retention time 3.65 min, M+H⁺=588.6 forformula C₃₅H₃₄N₅O₄. ¹H NMR (400 MHz, Methanol-d₄): d 2.95 (t, J=7.2 Hz,2H), 3.43 (t, J=7.2 Hz, 2H), 4.46 (s, 2H), 5.09 (s, 2H), 5.37 (s, 2H),6.64 (s, 1H), 7.13-7.29 (m, 9H), 7.38-7.41 (m, 3H), 7.47 (m, 4H), 7.70(d, J=8.4 Hz, 2H). ¹³C NMR (101 MHz, Methanol-d₄): d (ppm) 35.8, 43.7,45.4, 46.9, 70.6, 105.8, 114.9, 124.2, 124.6, 126.0, 127.2, 127.4,129.1, 129.6, 129.7, 129.8, 129.9, 130.0, 133.8, 137.8, 140.7, 160.2,170.3.

The product of Example 3 was synthesized in same way as described forcompound of Example 2 as a p-toluenesulfonic acid salt and an amorphoussolid. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.):retention time 3.18 min, M+H⁺=454.1 for formula C₂₇H₂₈N₅Q. ¹H NMR (400MHz, Methanol-d₄): d 2.32 (s, 3H), 3.03 (t, J=7.2 Hz, 2H), 3.56 (t,J=7.2 Hz, 2H), 4.48 (s, 2H), 5.14 (s, 2H), 7.19 (d, J=8.0 Hz, 4H),7.26-7.34 (m, 6H), 7.48 (d, J=8.0 Hz, 2H), 7.55 (s, 1H), 7.64 (d, J=7.6Hz, 1H), 7.69 (t, J=8 Hz, 4H), 8.72 (s, 2H), 9.18 (s, 2H). ¹³C NMR (101MHz, Methanol-d₄): d (ppm) 21.3, 34.3, 43.7, 46.8, 59.6, 115.4, 122.0,124.6, 126.9, 127.8, 128.2, 128.3, 129.0, 129.2, 129.5, 129.7, 129.8,129.9, 130.3, 131.4, 137.4, 138.9, 141.8, 146.7, 159.5, 168.2, 168.3,169.7.

Example 4

EX-4A) 2-[3-Amino-2-oxo-2H-quinolin-1-yl]acetic acid, (0.206 g, 0.81mmol) was treated with benzenesulfonyl chloride (0.172 g, 0.97 mmol) inpyridine for one hour. After removing the pyridine, the residue wasrecrystallized in acetone to yield a white crystal solid as the product,2-[3-benzenesulfonylamino-2-oxo-2H-quinolin-1-yl]acetic acid,(EX-4A)(0.117 g, y=41% ). HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Mn @ 254nm @ 50° C.): retention time 2.85 min, M+H⁺=359.2 for formulaC₁₇H₁₅N₂O₂S. ¹H NMR (400 MHz, Acetone-d₆): d 5.12 (s, 2H), 7.28 (t,J=7.2 Hz, 1H), 7.36 (d, J=8.8 Hz, 1H), 7.48-7.63 (m, 4H), 7.75 (dd, J=8,1.6 Hz, 1H), 7.74 (s, 1H), 8.00-8.03 (m, 2H). ¹³C NMR (101 MHz,Acetone-d₆): d (ppm) 44.8, 115.0, 120.8, 120.9, 123.9, 127.8, 128.1,129.4, 129.9, 130.1, 134.2, 136.7, 140.4, 158.2, 169.1.

EX-4B) Compound EX-4A was synthesized in same way as described forcompound EX-2A giving a white powder. HPLC-MS (0 to 95% AcCN/6 min @ 1.0mL/Min @ 254 nm @ 50° C.): retention time 3.23 min, M+H⁺=624.2 forformula C₃₃H₃₀N₅O₆S. ¹H NMR (400 MHz, Methanol-d₄): d 4.45 (s, 2H), 5.06(s, 2H), 5.38 (s, 2H), 7.24-7.60 (m, 14H), 7.71 (d, J=8.0 Hz, 2H), 7.8(s, 1H), 7.94 (d, J=7.2 Hz, 2H). ¹³C NMR (101 MHz, Methanol-d₄): d (ppm)43.7, 47.0, 70.7, 115.3, 121.7, 122.5, 124.5, 127.3, 128.4, 129.1,129.6, 129.7, 129.9, 130.0, 130.1, 130.2, 130.3, 134.4, 135.8, 137.2,140.8, 147.7, 154.6, 159.3, 167.9, 169.8.

Compound of this example was synthesized in same way as described forcompound Example 2. It is an amorphous off-white solid and ap-toluenesulfonic acid salt. HPLC-MS (5 to 95% AcCN/6 min @ 1.0 mL/Min @254 nm @ 50° C.): retention time 2.02 min, M+H⁺=490.1 for formulaC₂₅H₂₄N₅O₄S. ¹H NMR (400 MHz, Methanol-d₄): d 2.34 (s, 3H), 4.46 (s,2H), 5.06 (s, 2H), 7.20 (d, J=8.0 Hz, 1H), 7.24-7.29 (m, 2H), 7.46-7.51(m, 6H), 7.55 (d, J=7.2 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.71 (m, 4H),7.86 (s, 1H), 7.95 (d, J=8.0 Hz, 2H). ¹³C NMR (101 MHz, Methanol-d₄): d(ppm) 21.3, 43.6, 46.9, 115.1, 121.6, 122.4, 124.4, 126.8, 127.9, 128.2,128.9, 129.0, 129.5, 129.7, 130.1, 130.2, 134.3, 137.0, 140.6, 146.6,159.2, 169.5, 184.2.

Example 5

EX-5A) A solution of 2-amino pyridine (20.42 g, 217.0 mmol) indichloromethane 500 mL was cooled to 0° C. and treated with triethylamine (36.29 mL, 260.4 mmol) and pivaloyl chloride (28.06 mL, 227.8mmol). After 15 minutes, the reaction mixture was allowed to warm toroom temperature and stir overnight. The reaction mixture was pouredonto ice, and the organic layer was washed with saturated NaHCO₃ (aq),and dried over Na₂SO₄. The volatile components were removed, and a brownoil was isolated. Crystallization with hexanes afforded 31 g ofN-(pyrid-2-yl)-2,2-dimethylacetamide (EX-5A)as white crystals in 80%yield. Reference: Turner, J. A. J. Org. Chem. 1983, 48, 3401.

EX-5B) A solution of EX-5A (2.00 g, 11.23 mmol) in THF (115 mL) at −78°C. was treated with n-BuLi (14.1 mL, 28.10 mmol of a 2.0 M solution inhexanes). The reaction mixture was allowed to warm to 0° C. and stir for2 h. The reaction mixture was again cooled to −78° C., and the mixturewas quenched with DMF (2.18 mL, 28.10 mmol). The reaction mixture wasallowed to warm to room temperature and to stir overnight. The reactionmixture was poured into a slurry of ice and 6N HCl, and the acidifiedmixture was stirred for 15 minutes. The organic layer was separated(discard), and the aqueous layer was neutralized with K₂CO₃ andextracted with ether (3×100 mL). The combined organic layers were washedwith water, brine and dried over MgSO₄. After filtration and evaporationof the volatiles, a yellow oil was isolated which solidified uponstanding. 1.23 g (53%) of EX-5B product was isolated. Reference: Turner,J. A. J. Org. Chem. 1990, 55, 4744.

EX-5C) A mixture of EX-5B (0.62 g, 3.01 mmol) and 3N HCl (30 mL) wasrefluxed overnight. After the reaction mixture was allowed to cool toroom temperature, it was washed with ether (2×50 mL). The organic layerwas discarded. The aqueous layer was neutralized with K₂CO₃, andextracted with ether (4×50 mL). The combined ether layers were driedover K₂CO₃, filtered, and concentrated to afford2-aminopyridinecarboxaldehyde (EX-5C) as a yellow oil (0.36 g) whichsolidified upon standing. The crude material was used with any furtherpurification. Reference: Moormann, A. E.; Yen, C. H.; Yu, S. Syn.Commun. 1987, 17, 1695.

EX-5D) A mixture of hippuric acid (0.54 g, 3.01 mmol) and aceticanhydride (30 mL) was heated to 80° C. After 2 h, the reaction mixturewas homogeneous. The hot reaction mixture was treated with a solution ofEX-5C (0.37 g, 3.01 mmol) in acetic anhydride. After stirring thereaction mixture for an additional 16 h, the reaction mixture becameheterogeneous. The volatile components were removed in vacuo, and theprecipitate was filtered. The filter cake was washed with ether (3×30mL), and 0.36 g of 3-benzamido-2-oxo-2H-1,8-naphthyridine (EX-5D) wasisolated as tan colored powder in 45% yield: ¹H NMR (300 MHz, d-DMSO) d12.77 (s, 1H), 9.47 (s, 1H), 8.72 (s, 1H), 8.45 (d, J=3.42 Hz, 1H),8.21-8.18 (m, 1H), 7.95 (d, J=7.6 Hz, 2H), 7.66-7.54 (m, 3H), 7.28 (dd,J₁=4.6 Hz, J₂=4.8 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃) d 165.8, 159.4,149.2, 146.6, 136.6, 134.3, 133.0, 130.3, 129.61 (2C), 129.58, 127.9,120.2, 119.8, 115.7; HRMS (EI) calcd for C₁₅H₁₁N₃O₂ 266.0930, found266.0939.

EX-5E) A solution of EX-5D (0.072 g, 0.271 mmol) in DMF (5 mL) wascooled to 0° C., and NaH (60% dispersion in mineral oil, 0.013 g, 0.325mmol) was slowly added. After five minutes, methyl bromoacetate wasadded dropwise via syringe. The reaction mixture was allowed to warm toroom temperature, and it was stirred until no starting material remainedby TLC. DMF was removed in vacuo which afforded a yellow residue. Theresidue was triturated in water and washed with water and hexanes toafford 0.062 g of methyl2-[3-benzamido-2-oxo-2H-1,8-naphthyridin-1-yl]acetate (EX-5E) in 68%yield: ¹H NMR (400 MHz, CDCl₃) d 9.30 (s, 1H), 8.88 (s, 1H), 8.45 (d,J=4.6 Hz, 1H), 7.95-7.91 (m, 3H), 7.56-7.46 (m, 3H), 7.23-7.20 (m, 1H),5.37 (s, 2H), 3.74 (s,3H); ¹³C NMR (100 MHz, CDCl₃) d 168.8, 166.1,159.0, 148.0, 145.5, 136.5, 134.0, 132.6, 129.12, 129.11, 129.08, 128.8,127.4, 119.8, 119.0, 116.7, 52.7, 43.2; HRMS (EI) calcd for C₁₈H₁₅N₃O₄338.1156, found 338.1141.

EX-5F) A solution of EX-5E (0.053 g,0.157 mmol) in THF and methanol(3:2, 5 mL) was treated with 1.0 M LiOH (aq). The reaction mixture wasstirred over night. The mixture was concentrated to remove the volatilecomponents. The resulting aqueous solution was acidified with 1N HCl,and a solid precipitated from the solution. After filtration, the filtercake was washed with 1N HCl and water to afford 0.038 g of2-[3-benzamido-2-oxo-2H-1,8-naphthyridin-1-yl]acetcc acid (EX-5F) aswhite solid in 74% yield: ¹H NMR (400 MHz, d-DMSO) d 13.10 (br s, 1H),9.53 (s, 1H), 8.78 (s, 1H), 8.51-8.50 (m, 1H), 8.26 (d, J=7.8 Hz, 1H),7.93 (d, J=8.1 Hz, 2H), 7.62-7.51 (m, 3H), 7.36-7.32 (m, 1H), 5.14 (s,2H); ¹³C NMR (100 MHz, d-DMSO) d 169.9, 166.0, 158.7, 148.8, 145.9,137.5, 134.2, 133.0, 129.5 (2C), 128.8, 128.0 (2C), 120.4, 120.2, 116.2,43.5; HRMS (EI) calcd for C₁₇H₁₃N₃O₄ 324.1004, found 324.098.

EX-5G) A solution of EX-5F (0.099 g, 0.30 mmol) in 3 mL of DMF wastreated with N-hydroxybenzotriazole (0.054 g, 0.40 mmol), and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.076 g,0.40 mmol), and N,N-diisopropylethylamine (0.37 mL, 2,14 mmol). Theresulting mixture was allowed to stir for 15 minutes at roomtemperature. The reaction mixture was then treated with4(N-Cbz-amidino)benzylamine (0.127 g, 0.40 mmol) as a solution in DMF (3mL). The resulting reaction mixture was allowed to stir for 18 hours.The reaction mixture was partitioned between ethyl acetate and asaturated NH₄Cl(aq) solution. The separated organic layer was washedwith saturated K₂CO₃ (aq), saturated NH₄Cl (aq), and brine. The organicsolution was dried (Na₂SO₄), filtered and concentrated. (EX-5G) wasisolated as a white solid, and the crude product was used in the nextstep without further purification: HRMS (EI) calcd for C₃₃H₂₈N₆O₅589.2178, found 589.2199.

A solution of Cbz-amidine (EX-5G) (0.090 g,0.15 mmol) in 6 mL ofmethanol, and 1 mL of 4 N HCl in dioxane was treated with 25 mg of 10%Pd/C in one portion. The resulting reactin mixture was stirred underhydrogen gas (25 psi) for 18 hours. After filtration of the reactionmixture through a pad of Celite, the solvent was removed under reducedpressure. Slow addition of 1 M HCl precipitated pure product of theinvention as a white solid: ¹H NMR (400 MHz, d-DMSO) d 9.52 (s, 1H),9.24 (s, 2H), 8.91-8.83 (m, 2H), 8.77 (s, 1H), 8.53-8.52 (m, 1H), 8.27(d, J=7.5 Hz, 1H), 7.93 (d, J=7.5 Hz, 2H), 7.73 (d, J=8.3 Hz, 2H),7.63-7.61 (m, 1H), 7.56-7.52 (m, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.37-7.34(m, 1H), 5.17 (s, 2H), 4.35 (d, J=5.9 Hz, 2H); ¹³C NMR (100 MHz, d-DMSO)d 167.7, 166.0, 165.9, 159.0, 148.6, 146.4, 146.2, 137.4, 134.2, 133.1,129.6, 128.9, 128.8, 127.93 (2C), 127.88 (2C), 127.0, 120.21, 120.16,116.5, 72.9, 60.9, 44.8, 42.4; HRMS (EI) calcd for C₂₅H₂₂N₆O₃ 455.1832,found 455.1840.

Additional substitutedN-[Substituted]-(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamidescan be prepared by one skilled in the art using methods similar to thoseabove. These acetamides as shown in Example Table 1. EXAMPLE TABLE 1N-[Substituted]-(3-benzylsulfonylamino-2-oxo-2H-quinolin-1-yl)acetamides.

Ex.No. Y⁰ 6 2-[4-Aminophenyl]ethyl 7 4-aminobutyl 8 5-aminopentyl 96-(N,N-dimethylamino)hexyl 10 4-Aminomethylbenzyl 11 3-Aminomethylbenzyl12 3-[Imidazo-1-yl]propyl 13 2-[Imidazo-5-yl]ethyl 142-[Pyrid-3-yl]ethyl 15 3-[N-Methylpiperidin-4-yl]propyl 16 4-Aminobenzyl

The pyridone analogs of the present invention have the general structureas shown in FIG. 2.

The general synthetic route is illustrated in Scheme 3 whereinsubstituents are as defined herein. These compounds are exemplified inExamples 17 through 23.

Example 17

N-[[2(S)-2-[1-hydroxy-1-(2-thiazolyl)]-5-[[[(4-methoxy-2,3,6-trimethyl)sulfonylamino]iminomethyl]amino]pentyl]-6-(2-phenylethyl)-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetamide(0.084 g, 0.098 mmol) was treated with1,3-dihydro-1-hydroxy-3,3-bis(trifluoromethyl)-1-oxide-1,2-benziodoxole(0.0588 g, 0.147 mmole) in 1 ml acetonitrile. Similar work-up procedureas in preparing EX-1E was used to yield the oxidation product. Theoxidation product was treated with thioanisole (0.073 g, 0.59 mmol) and3 ml trifluoroacetic acid for 6 hours. After removing the TFA, theresidue was triturated in ether. It was purified by a preparative C-18reverse HPLC column using a gradient that proceed from 5% to 95%acetonitrile in H₂O in the presence of 0.1% TFA in 30 minutes to yieldthe product,N-[[2(S)-2-[1-Oxo-1-(2-thiazolyl)]-5-[[[(amino)iminomethyl]amino]pentyl]-6-(2-phenylethyl)-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetamidetrifluoroacetic acid salt, as a white amorphous solid (0.0232 g, y=31%).HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retentiontime 3.43 min, M+H⁺=650.2 for formula C₃₁H₃₅N₇O₅S₂.

Example 18

This compound,N-[[2(S)-2-[1-Oxo-1-(2-thiazolyl)]-5-[(amino)iminomethyl)-amino]pentyl]-6-methyl-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetamidetrifluoroacetic acid salt, was prepared in a similar fashion as forExample 1. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.):retention time 2.69 min, M+H⁺⁺=560.3 for formula C₂₄H₂₉N₇O₅S₂.

Example 19

The compound,N-[[4-(amino)iminomethyl]phenyl]methyl]-6-(2-phenylethyl)-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetamaidep-toluenesulfonic acid salt, was synthesized in a similar fashion as forExample 2 using 6-(2-phenylethyl)-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetic acid as starting material. HPLC-MS(0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time3.23 min, M+H⁺=558.5 for formula C₃₀H₃₁N₅O₄S. ¹H NMR (400 MHz, CD₃0D): δ2.36 (s, 3H), 2.92 (bm, 4H), 4.43 (s, 2H), 4.54 (s, 2H), 4.87 9s, 2H),6.10 (d, J=8.0 Hz, 1H), 7.21 (m, 5H), 7.26-7.31 (m, 8H), 7.55 (d, J=8.4Hz, 2H), 7.69 (d, J=8.0 Hz, 2H), 7.71 (d, J=8.0 Hz, 2H).

Example 20

This compound,N-[[4[-(amino)iminomethyl]phenyl]methyl]-6-methyl-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineacetamidep-toluenesulfonic acid salt, was synthesized in a similar fashion as forExample 2 using6-methyl-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineaceticacid as starting material. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @254 nm @ 50° C.): retention time 2.41 min, M+H⁺=468.1 for formulaC₂₃H₂₅N₅O₄S. ¹H NMR (400 MHz, CD₃OD): δ 2.34 (s, 3H), 2.36 (s, 3H), 4.43(s, 2H), 4.53 (s, 2H), 4.87 (s, 2H), 6.15 (d, J=7.6 Hz, 1H), 7.21-7.31(m, 8H), 7.56 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.0 Hz, 2H), 7.72 (d, J=8.0Hz, 2H), 8.70 (b, 1H), 9.19 (b, 1H).

Example 21

This compound was synthesized in a similar fashion as for Example 2using6-(2-phenylethyl)-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineaceticacid as starting material and coupling it with4-[1-(N,N-bis-Boc-amidino)piperidinyl]methylamine The coupling productwas treated with 4N HCl in dioxane to generate the product. Thecompounds were purified by reverse phase C-18 HPLC to generate the finalpure products. HPLC-MS (0 to 95% AcCN/6 min @P 1.0 mL/Min @ 254 nm @ 50°C.): retention time 3.10 min, M+H⁺=565.6 for formula C₂₉H₃₇N₆O₄S.

Example 22

This compound was synthesized in a similar fashion as for Example 2using6-methyl-2-oxo-3-[[(phenylmethyl)sulfonyl]amino]-1(2H)-pyridineaceticacid as starting material and coupling it with4-[1-(N,N-bis-Boc-amidino)piperidinyl]methylamine The coupling productwas treated with 4N HCl in dioxane to generate the product. Thecompounds were purified by reverse phase C-18 HPLC to generate the finalpure products. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50°C.): retention time 2.42 min, M+H⁺=475.3 for formula C₂₂H₃₁N₆O₄S .

One subclass of pyridone analogs have a heteroaryl group substitutingthe pyridone ring at the 5 or 6 position. Scheme 4 illustrates a processto prepare heteroaryl substituted pyridones. The preparation procedureis exemplified in Example 23 for the preparation of a &substitutedpyridyl group although it will be readily recognized that a wide varietyof substituted pyridines and other 5 and 6 membered heteroaryl groupscan be introduced using the procedure described below.

Example 23

EX-23A) One equivalent of commercially available 4-acetylpyridine istreated with three equivalents N,N-dimethylformamide dimethyl acetal inrefluxing acetonitrile for 12 hours. After removing the solvent andexcess amount of N,N-dimethylformamide dimethyl acetal, the resultingyellow solid is dissolved in DMF. To this solution is added oneequivalent cyanoacetamide and two equivalents of sodium methoxide. Theresulting mixture is heated at 100° C. for 5 hours. After cooling down,the reaction mixture is mixed with water and acidified with HCl to pH 5.The resulting yellow precipitate is filtered, washed with water anddried via vacuum to give the product EX-23A as a yellow solid.

EX-23B) Compound EX-23A is heated to reflux in one portion of 48%aqueous HBr and two portions of acetic acid for 12 hours. After themixture is cooled down, mixed with water and adjusted the pH to 5, alight yellow precipitate is formed. The light yellow precipitate isfiltered and washed with 1N HCl and water, dried via vacuum to give theproduct EX-23B as an off-white solid.

EX-23C) Compound EX-23B is treated with 1.1 equivalent of DPPA, 1equivalent triethylamine in dioxane at refluxing temperature for twohours. Five equivalents t-butanol is added into the mixture, and themixture is then refluxed overnight. After removing the solvent, theremaining residue is worked up by standard aqueous work-up procedure.The residue is then purified by silica gel column chromatography toyield Compound EX-23C.

EX-23D) Compound EX-23C is mixed with one equivalent sodium hydride inDMF and one equivalent methyl bromoacetate subsequently. After stirringat ambient temperature for 12 hours, the reaction is worked up bystandard procedure. The product EX-23D is purified by silica gel columnchromatography.

EX-23E) Compound EX-23D is treated with 50% TFA in dichloromethane for 1hour. After removing the solvent and TFA, the residue is redissolved inTMF with one equivalent of triethylamine. To this solution is added oneequivalent phenylacetaldehyde and two equivalents sodiumtriacetoxyborohydride. After stirring for 12 hours, the reaction isquenched with addition of aqueous ammonium chloride. Standard aqueouswork-up and silica gel column chromatography yields the desired productEX-23E.

EX-23F) Compound EX-23E is treated with 1M LiOH in 1:1:1 ratio of THF,methanol and water for half hour. After it is acidified with 1N HCl, theorganic solvent is removed and a precipitate will form. The precipitateis filtered, washed with water and dried by vacuum to give the desiredproduct EX-23F. Compound EX-23F is treated with one equivalent EDC andHOBt in the presence of three equivalents diisopropylethyl amine in DMFfor 10 minutes. One equivalent of 4-aminomethylbenzarnidine, which isprotected with Cbz at the amidine, is then added into the reactionmixture. After stirring at ambient temperature for four hours, thereaction mixture is worked up by standard procedure and the productEX-23G is purified by silica gel column chromatography.

Compound EX-23G is dissolved in methanol in the presence of 5equivalents of HCl and 5% equivalent of 10% Pd/C. The mixture is stirredunder an atmosphere of hydrogen (ambient pressure) for five hours. Afterfiltration and removing the solvent, Compound 23 is obtained as the pureproduct.

In a related procedure, 5-substituted pyridones can be prepared asillustrated in Examples 24 and 25.

Example 24

EX-24A) 3-Nitro-2-hydroxylpyridine (49.5 g, 0.35 mol) and 10% Pd/C (4.21g, 4 mmol) in 500 ml ethanol was stirred under an atmosphere of hydrogenintroduced via a balloon for 24 hours. After filtering through a pad ofCelite 545 and removing the ethanol, a brown solid was obtained as thepure product, 3-aminopyrid-2-one, (38 g, 97%). HPLC-MS (0 to 30% AcCN/6min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time 0.097 min,M+H⁺=111.1 for formula C₅H₇N₂O.

EX-24B) Compound EX-24A (27.25 g, 0.248 mol) was treated with Bocanhydride (59.47 g, 0.272 mol), triethylamine (52 ml, 0.372 mol) andDMAP (1.5 g, 12.4 mmol) in 500 ml DCM for 4 hours. After an aqueouswork-up and removing the solvent, the residue was passed through a shortsilica gel plug using 40% ethylacetate in hexane as eluent to yield thecrude product (28 g, 56% 0. Pure product, 3-(N-Boc-amino)pyrid-2-one,was obtained by recrystallization in acetone as a needle-like whitecrystalline solid. HPLC-MS (0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @50° C.): retention time 2.39 min, M-Boc +H⁺=111.1 for formula C₅H₇N₂O.¹H NMR (400 MHz, CDCl₃): d 1.52 (s, 9H), 6.32 (t, J=7.2 Hz, 1H), 7.00(dd, J=6.4, 1.6 Hz, 1H), 7.55 (s, 1H), 8.10 (d, J=6.4 Hz, 1H), 12.86(b,1H). ¹³C NMR (101 MHz, CDCl₃): d 28.2, 80.8, 107.7, 121.8, 125.2, 129.7,152.7, 158.8.

EX-24C) Compound EX-24B (13.58 g, 64.6 mmol) and N-iodosuccinimide (21.8g,97 mmol) in 250 ml dichloromethane was stirred at room temperature for18 hours. After filtration to remove the by-product succinimide, thesolvent was removed under reduced pressure. The remaining residue wassubjected to a silica gel flash chromatography to yield a brown solid asthe product, 3-(N-Boc-amino)-5-iodopyrid-2-one, (17.3 g, 80%). HPLC-MS(0 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time3.22 min, M+Na⁺=359.0 for formula C₁₀H₁₂IN₂O₃Na.

EX-24D) Compound EX-24C (9.62 g, 28.6 mmol) was treated with sodiumhydride (1.71 g, 42.9 mmol) 60% in mineral oil in 200 ml THF for 10minutes. To this mixture was added methyl bromoacetate (4.33 ml, 45.8mmol). The resulting structure was stirred at room temperature for 1hour. After removing the THF, the residue was washed with hexanes toremove the mineral oil. It was then partitioned between ethylacetate andsaturated aqueous ammonium chloride. The organic layer was washed withsaturated aqueous ammonium chloride three times and dried over anhydrousMgSO₄. After removing the solvent, a yellow amorphous solid was obtainedas the product, methyl2-[3-(N-Boc-amino)-5-iodo-2-oxopyrid-2-yl]acetate, (11.1 g, 95%).

EX-24E) 3-Pyridyl boronic acid (2.0 g, 4.93 mmol) was suspended in 80 mltoluene and the mixture was degassed by bubbling nitrogen through for 10minutes. Tetrakis-(triphenyl)phosphine Palladium (0.54 g, 0.46 mmol) wasdissolved in a pre-degassed mixture of 20 ml toluene and 50 ml methanol.The catalyst solution was added to the boronic acid solution undernitrogen. To this resulting mixture was added compound EX-24D (3.80 g,9.31 mmol) in 25 ml methanol followed with 22 ml 2M Na₂CO₃ solution. Thereaction solution was heated to reflux for 2.5 hours. After it wascooled down to room temperature, it was mixed with 10 ml 2.5N NaOH andwas stirred for an half hour. After removing all the solvent, theremaining residue was re-dissolved in methanol and the pH of thesolution was adjusted to 6 with 1 N HCl. After removing all the solvent,the residue was absorbed on silica gel and subjected to silica gel flashchromatography using 5% methanol in DCM as the eluate. The pure product,methyl 2-[3-(N-Boc-amino)-5-(pyrid-3-yl)-2-oxopyrid-2-yl]acetate(EX-24E), was obtained as a white amorphous solid (1.01 g, 57%). HPLC-MS(5 to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time1.89 min, M+H⁺=346.0 for formula C₁₇H₁₉N₃O₅. ¹H NMR (400 MHz, CDCl₃): d1.53 (s, 9H), 4.82 (s, 2H), 7.62 (d, J=2.4 Hz, 1H), 7.87 (t, J=6.0, 1H),8.36 (s, 1H), 8.47 (d, J=8.4 Hz, 1H), 8.68 (d, J=4.4 Hz, 1H), 9.05 (s,1H). ¹³C NMR (101 MHz, CDCl₃): d 28.0, 50.9, 81.6, 113.8, 117.3, 126.5,128.9, 130.4, 136.4, 139.8, 140.4, 140.6, 152.7, 156.6, 169.0.

Starting with the intermediate EX-24E, the final inhibitor compound issynthesized in a similar fashion as described in other examples byprocedures described above.

Example 25

EX-25A) 3-Nitrobenzeneboronic acid (1.41 g, 8.43 mmol) was suspended in50 ml dioxane and the mixture was degassed with nitrogen.Tetrakis-(triphenyl)phosphine Palladium (0.406 g, 0.35 mmol) dissolvedin 10 ml dioxane was added to the boronic acid solution under nitrogen.To this mixture was added compound EX-24D (2.87 g, 7.03 mmol) and 7 ml2M potassium phosphate solution. The reaction mixture was heated toreflux for 3 hours. After removing the dioxane, the remaining residuewas partitioned between ethylacetate and aqueous saturated ammoniumchloride. The organic layer was washed with aqueous saturated ammoniumchloride and dried over sodium sulfate. The pure product was isolated bya silica gel column flash chromatography to yield a yellow crystallinesolid (1.13 g, 40%). The product, methyl2-[3-(N-Boc-amino)-5-(3-nitrophenyl)-2-oxopyrid-2-yl]acetate, showed onepeak on LC-MS. However, it is a mixture of two isomers with a ratio of2.8 to 1 based on ¹H NMR and ¹³C NMR. One isomer has the nitro group atthe same side of the Boc amino group, the other in the oppositedirection. The NMR data only lists the dominant isomer here. HPLC-MS (5to 95% AcCN/6 min @ 1.0 mL/Min @ 254 nm @ 50° C.): retention time 3.74min, M+Na⁺=426.3 for formula C₁₉H₂₁N₃O₇Na. ¹H NMR (400 MHz, CDCl₃): d1.50 (s, 9H), 3.82 (s, 3H), 4.80 (s, 2H), 7.20 (d, J=2.4 Hz, 1H), 7.56(t, J=8.0, 1H), 7.66 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 8.15 (d, J=8.0 Hz,1H), 8.28 (d, J=2.4 Hz, 1H), 8.36 (s, 1H).

Starting with the intermediate EX-25A, the final inhibitor compound issynthesized in a similar fashion as described in other examples byprocedures described above.

Preparation of sulfonyl analogs of pyridones of the present invention inwhich a sulfonyl replaces the carbonyl group of the N-1 acetamide sidechain can be accomplished by use of the general procedure in Scheme 3.Example 26, a specific example of a sulfonamide of the presentinvention, is synthesized as according to the general procedure shown inScheme 5.

Example 26

Compound EX-26C can be prepared using same methods as described inExample 23 for compounds EX-23A, EX-23B, and EX-23C.

EX-26D) Compound EX-26C is treated with 1.1 equivalent NaH and 1.5equivalents sodium bromomethanesulfonate in DMF overnight. The reactionis quenched by dilution with water and addition of 1N HCl to adjust thereaction solution to a pH of 3 to precipitate the product. The crudeproduct is obtained by filtration and washing with water and ether. Thepure product EX-26D is further purified by recrystallization in ethanol.

EX-26E) Compound EX-26D is treated with 50% TFA in dichloromethane for 1hour. After removing the solvent and TFA, the residue is redissolved inTHF/Methanol with one equivalent of triethylamine. To this solution isadded one equivalent phenylacetaldehyde and two equivalents sodiumtriacetoxyborohydride. After stirring for 12 hours, the reaction isquenched with addition of aqueous ammonium chloride. Standard aqueouswork-up and silica gel column chromatography yields the desired productEX-26E.

EX-26F) Compound EX-26E is treated with one equivalent PCl₅ in toluenefor an half hour. One equivalent of 4-aminomethylbenzamidine, which isprotected with Cbz at the amidine, is then added into the reactionmixture followed with the addition of five equivalents pyridine. Themixture is allowed to be stirred for 12 hours. The reaction mixture isworked up by standard procedure and the product EX-26F is purified bysilica gel column chromatography.

Compound 26 is prepared from EX-26F using the procedure for compound 23in Example 23.

Preparation of methylene analogs of pyridones of the present inventionin which a methylene replaces the carbonyl group of the N-1 acetamideside chain can be accomplished by using the essential features of thegeneral procedure in Scheme 3. Example 27, a specific example of anethyleneamine of the present invention, can be synthesized as shownspecifically in Scheme 6.

Example 27

EX-27A) To a ether solution of pyridinylacetate ester with the B-A groupadded, diisobutylaluminum hydride (5 eq.) is added at −78° C. After 30minutes stirring, methanol is added to quench the reaction. Theresulting mixture is poured into a saturated aqueous solution ofRochelle salt. The layers are separated, and the aqueous layer isextracted with ethyl ether. The combined extract is dried over MgSO₄,and the solvent is evaporated to dryness. The remaining residue issubjected to a silica gel column chromatography to yield the pureproduct aldehyde (EX-27A).

EX-27B) Compound EX-27A is mixed with one equivalent of Cbz protected4-amidinobenzylamine and two equivalents sodium triacetoxyborohydride inTHF. The reaction mixture is worked up according to the standardprocedure. The product EX-27B is purified by silica gel columnchromatography.

Compound EX-27B is first treated with 4N HCl in dioxane for 4 hours.After removing the dioxane, the residue is re-dissolved in methanol inthe presence of 5 equivalents of HCl and 5% equivalent of 10% Pd/C. Themixture is stirred under an atmosphere of hydrogen (ambient pressure)for five hours. After filtration and removing the solvent, the compoundis obtained as the pure product.

Another subclass of pyridone analogs have the general structure as shownin FIG. 3. Substituents are defined as disclosed herein. Z⁰ can beheteroatoms such as S, O, N, and others. The synthesis of this subclassof pyridone analogs is exemplified as in the synthesis of Example 28 assummarized in Scheme 7.

Example 28

EX-28A) Commercially available compound 2-amino-3-nitro-6-chloropyridineis reacted with one equivalent of phenylthiol in the presence of sodiumcarbonate in DMF at 80° C. After the completion of the reaction, thereaction mixture is mixed with water. Filtration yields the crudeproduct EX-28A that can be purified by recrystallization in methanol.

EX-28B) Compound EX-28A is dissolved in 12N H₂SO₄, and the solution istreated with aqueous solution of NaNO₂ (3 eq.) firstly at 0° C., then at100° C. Dilution with water precipitates the product. Filtration andwashing with water and ether yields the crude product EX-23B that can befurther purified by recrystallization in ethanol.

EX-28C) Compound EX-28B is mixed with one equivalent sodium hydride inDMF and one equivalent methyl bromoacetate subsequently. After stirringat ambient temperature for 12 hours, the reaction is worked up bystandard procedure. The product EX-28C is purified by silica gel columnchromatography.

EX-28D) Compound EX-28C is dissolved in methanol in the presence of 5%equivalent of 10% Pd/C. The mixture is stirred under an atmosphere ofhydrogen (ambient pressure) for an half hour. After filtration andremoving the solvent, Compound EX-28D is obtained as the pure product.

Example compound 28 can be prepared from EX-28D in a similar fashion asdescribed in the preparation of compounds EX-23E, EX-23F, EX-23G and 23.

Formula (I) compounds of this invention possessing hydroxyl, thiol, andamine functional groups can be converted to a wide variety derivatives.Alternatively, derivatized Formula (I) compounds can be obtained byfirst derivatizing one or more intermediates in the processes ofpreparation before further transforming the derivatized intermediate tocompounds of Formula (I). A hydroxyl group in the form of an alcohol orphenol can be readily converted to esters of carboxylic, sulfonic,carbamic, phosphonic, and phosphoric acids. Acylation to form acarboxylic acid ester is readily effected using a suitable acylatingreagent such as an aliphatic acid anhydride or acid chloride. Thecorresponding aryl and heteroaryl acid anhydrides and acid chlorides canalso be used. Such reactions are generally carried out using an aminecatalyst such as pyridine in an inert solvent. Similarly, carbamic acidesters (urethanes) can be obtained by reacting a hydroxyl group withisocyanates and carbamoyl chlorides. Sulfonate, phosphonate, andphosphate esters can be prepared using the corresponding acid chlorideand similar reagents. Compounds of Formula (I) that have at least onethiol group present can be converted to the corresponding thioestersderivatives analogous to those of alcohols and phenols using the samereagents and comparable reaction conditions. Compounds of Formula (I)that have at least one primary or secondary amine group present can beconverted to the corresponding amide derivatives. Amides of carboxylicacids can be prepared using the appropriate acid chloride or anhydrideswith reaction conditions analogous to those used with alcohols andphenols. Ureas of the corresponding primary or secondary amine can beprepared using isocyanates directly and carbamoyl chlorides in thepresence of an acid scavenger such as triethylamine or pyridine.Sulfonamides can be prepared from the corresponding sulfonyl chloride inthe presence of aqueous sodium hydroxide or a tertiary amine. Suitableprocedures and methods for preparing these derivatives can be found inHouse's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner,Fuson, and Curtin in The Systematic Identification of Organic Compounds,5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents forOrganic Synthesis, Volume 1, John Wiley & Sons. Reagents of a widevariety that can be used to derivatize hydroxyl, thiol, and amines ofcompounds of Formula (I) are available from commercial sources or thereferences cited above, which are incorporated herein by reference.

Formula (I) compounds of this invention possessing hydroxyl, thiol, andamine functional groups can be alkylated to a wide variety ofderivatives. Alternatively, alkylated Formula (I) compounds can beobtained by first alkylating one or more intermediates in the processesof preparation before further transforming the alkylated intermediate tocompounds of Formula (I). A hydroxyl group of compounds of Formula (I)can be readily converted to ethers. Alkylation to form an ether isreadily effected using a suitable alkylating reagent such as an alkylbromide, alkyl iodide or alkyl sulfonate. The corresponding aralkyl,heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl, and heteroaralkyloxyalkylbromides, iodides, and sulfonates can also be used. Such reactions aregenerally carried out using an alkoxide forming reagent such as sodiumhydride, potassium t-butoxide, sodium amide, lithium amide, and n-butyllithium using an inert polar solvent such as DMF, DMSO, THF, andsimilar, comparable solvents. amine catalyst such as pyridine in aninert solvent. Compounds of Formula (I) that have at least one thiolgroup present can be converted to the corresponding thioetherderivatives analogous to those of alcohols and phenols using the samereagents and comparable reaction conditions. Compounds of Formula (I)that have at least one primary, secondary or tertiary amine grouppresent can be converted to the corresponding secondary, tertiary orquaternary ammonium derivative. Quaternary ammonium derivatives can beprepared using the appropriate bromides, iodides, and sulfonatesanalogous to those used with alcohols and phenols. Conditions involvereaction of the amine by warming it with the alkylating reagent with astoichiometric amount of the amine (i.e., one equivalent with a tertiaryamine, two with a secondary, and three with a primary). With primary andsecondary amines, two and one equivalents, respectively, of an acidscavenger are used concurrently. Secondary or tertiary amines can beprepared from the corresponding primary or secondary amine. A primaryamine can be dialkylated by reductive amination using an aldehyde, suchas formaldehyde, and sodium cyanoborohydride in the presence of glacialacetic acid. A primary amine can be monoalkylated by firstmono-protecting the amine with a ready cleaved protecting group, such astrifluoroacetyl. An alkylating agent, such as dimethylsulfate, in thepresence of a non-nucleophilic base, such as Barton's base(2-tert-butyl-1,1,3,3-tetramethylguanidine), gives the monomethylatedprotected amine. Removal of the protecting group using aqueous potassiumhydroxide gives the desired monoalkylated amine. Additional suitableprocedures and methods for preparing these derivatives can be found inHouse's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner,Fuson, and Curtin in The Systematic Identification of Organic Compounds,5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents forOrganic Synthesis published by John Wiley & Sons. Perfluoroalkylderivatives can be prepared as described by DesMarteau in J. Chem. Soc.Chem. Commun. 2241 (1998). Reagents of a wide variety that can be usedto derivatize hydroxyl, thiol, and amines of compounds of Formula (I)are available from commercial sources or the references cited above,which are incorporated herein by reference.

Assays for Biological Activity TF-VIIa Assay

In this assay 100 nM recombinant soluble tissue factor and 2 nMrecombinant human factor VIIa are added to a 96-well assay platecontaining 0.4 mM of the substrate,N-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline and either inhibitor orbuffer (5 mM CaCl₂, 50 mMTris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). Thereaction, in a final volume of 100 ul is measured immediately at 405 nmto determine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of TF-VIIa activity iscalculated from OD_(405nm) value from the experimental and controlsample.

Xa Assay

0.3 nM human factor Xa and 0. 15 mMN-α-Benzyloxycarbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride(S-2765) are added to a 96-well assay plate containing either inhibitoror buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction,in a final volume of 100 ul is measured immediately at 405 nm todetermine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of Xa activity iscalculated from OD_(405nm) value from the experimental and controlsample.

Thrombin Assay

0.28 nM human thrombin and 0.06 mMH-D-Phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline dihydrochlorideare added to a 96-well assay plate containing either inhibitor or buffer(50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in afinal volume of 100 ul is measured immediately at 405 nm to determinebackground absorbance. The plate is incubated at room temperature for 60min, at which time the rate of hydrolysis of the substrate is measuredby monitoring the reaction at 405 nm for the release of p-nitroaniline.Percent inhibition of thrombin activity is calculated from OD_(405nm)value from the experimental and control sample.

Trypsin Assay

5 ug/ml trypsin, type IX from porcine pancreas and 0.375 mMN-α-Benzoyl-L-arginine-p-nitroanilide (L-BAPNA) are added to a 96-wellassay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH8.0, 100 mM NaCl, 0.1% BSA). The reactions, in a final volume of 100 ulare measured immediately at 405 nm to determine background absorbance.The plate is incubated at room temperature for 60 min, at which time therate of hydrolysis of the substrate is measured by monitoring thereaction at 405 nm for the release of p-nitroaniline. Percent inhibitionof trypsin activity is calculated from OD405 nm value from theexperimental and control sample.

Recombinant soluble TF, consisting of amino acids 1-219 of the matureprotein sequence was expressed in E. coli and purified using a Mono QSepharose FPLC. Recombinant human VIIa was purchased from AmericanDiagnostica, Greenwich Conn. and chromogenic substrateN-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline was prepared by AmericanPeptide Company, Inc., Sunnyvale, Calif. Factor Xa was obtained fromEnzyme Research Laboratories, South Bend Ind., thrombin from Calbiochem,La Jolla, Calif., and trypsin and L-BAPNA from Sigma, St. Louis Mo. Thechromogenic substrates S-2765 and S-2238 were purchased fromChromogenix, Sweden.

The biological activity of the compounds of Examples 1 through 22 asdetermined by the bioassay procedures is summarized in the Table 1.TABLE 1 Inhibitory Activity of Pyridones toward Factor Xa, TF-VIIA,Thrombin II, and Trypsin II. Thrombin Factor Trpysin TF-VIIA II Xa IIExample IC50 IC50 IC50 IC50 Number (uM) (uM) (uM) (uM) 1 4.6 0.7 0.070.21 2 46 5.5 7.7 0.5 3 26.1 11.0 >30 0.86 4 >30 22.7 23.1 0.48 5 40%40% 27% — 6 >30 >30 >30 >30 7 >30 >30 >30 >30 8 >30 >30 >30 >309 >30 >30 >30 >30 10 >30 >30 >30 >30 11 >30 >30 >30 >3012 >30 >30 >30 >30 13 >30 >30 >30 >30 14 >30 >30 >30 >3015 >30 >30 >30 >30 16 >30 >30 >30 >30 17 1.1 0.2 0.1 0.3 18 0.8 <0.04<4.0 0.2 19 18.0 0.4 4.1 <0.1 20 23.0 0.3 5.7 0.5 21 >30 0.5 17 0.622 >30 <0.04 >0 11.1

1-8. (canceled)
 9. A compound having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is theFormula:

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,carboxamido, cyano, and Q^(b); A is selected from the group consistingof single covalent bond and (CH(R¹⁵))_(pa)—(W⁷)rr wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 3, and W⁷ is selected from the group consisting of (R⁷)NC(O) andN(R⁷); R⁷ is selected from the group consisting of hydrido, hydroxy andalkyl; R¹⁵ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl; R¹ and X^(O) are independently selected from thegroup consisting of hydrido, hydroxy, hydroxyamino, amidino, amino,cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is selectedfrom the group consisting of a covalent single bond, O, S, NH, and CH₂;Q is selected from the group consisting of aryl and heteroaryl wherein(a) a ring carbon in a first alpha position relative to the ring carbonat the point of attachment is optionally substituted by R⁹, (b) a ringcarbon in a second alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R¹³, (c) a ring carbon,in a first beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, andcyano; R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,amidocarbonyl, halo, haloalkyl, and cyano; Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, and C(NR²⁵)NR²³R²⁴, with the provisosthat no more than one of R²⁰ and R²¹ is hydroxy and that no more thanone of R²³ and R²⁴ is hydroxy; R²⁰, R²¹, R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido, alkyl, andhydroxy; and Q^(s) is selected from the group consisting of a singlecovalent bond, CH₂, and CH₂CH₂.
 10. The compound as recited in claim 9or a pharmaceutically acceptable salt thereof, wherein; B is theFormula:

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy,isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b); A is selected from the group consisting of single covalentbond, NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂; R¹ and X^(O) areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰-Q; Z⁰ isselected from the group consisting of a covalent single bond, O, S, NH,and CH₂; Q is selected from the group consisting of phenyl and2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl heteroaryl rings, wherein (a aring carbon in a first alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R⁹, (b) a ring carbonin a second alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydride, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; Q^(b) is selected from the group consisting of hydrido andC(NR²⁵)NR²³R²⁴, with the proviso that no more than one of R²³ and R²⁴ ishydroxy; R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, methyl, ethyl, and hydroxy; and Q^(s) is selectedfrom the group consisting of a single covalent bond, CH₂ and CH₂CH₂. 11.The compound as recited in claim 10 or a pharmaceutically acceptablesalt thereof, wherein; B is selected from the group consisting of2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl,4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl,3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl,4-methylphenyl, phenyl, and 3-trifluoromethylphenyl; A is selected fromthe group consisting of CH₂, CH₃CH, CF₃CH, NHC(O), CH₂CH₂,and CH₂CH₂CH₂;R¹ and X^(O) are independently selected from the group consisting ofhydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl,methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro; R² isZ⁰-Q; Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂; Q is selected from the group consisting of5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydrido, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂.
 12. The compound as recited in claim 9 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is theFormula:

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,carboxamido, cyano, and Q^(b); A is selected from the group consistingof single covalent bond and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 3, and W⁷ is N(R⁷); R⁷ is selected from the group consisting ofhydrido and alkyl; R¹⁵ is selected from the group consisting of hydrido,halo, alkyl, and haloalkyl; R¹ and X^(O) are independently selected fromthe group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino,cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is acovalent single bond; Q is selected from the group consisting of aryland heteroaryl wherein (a) a ring carbon in a first alpha positionrelative to the ring carbon at the point of attachment is optionallysubstituted by R⁹, (b) a ring carbon in a second alpha position relativeto the ring carbon at the point of attachment is optionally substitutedby R¹³, (c) a ring carbon, in a first beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R⁹, is optionally substituted byR¹⁰, (d) a ring carbon, in a second beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹³, is optionally substitutedby R¹², and (e) a ring carbon, if present, in the gamma positionrelative to the ring carbon at the point of attachment and in an alphaposition relative to each of the ring atoms optionally substituted byR¹⁰ and R¹², respectively, is optionally substituted by R¹¹; R⁹, R¹¹,and R¹³ are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ isformula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵ D⁶, J⁵, and J⁶ are N; R¹⁶, R¹⁷,R¹⁸, and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, and C(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴,and R²⁵ are independently selected from the group consisting of hydridoand alkyl; and Q^(s) is CH₂.
 13. The compound as recited in claim 12 ora pharmaceutically acceptable salt thereof, wherein; B is the Formula:

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methylthio,ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q^(b); A is selectedfrom the group consisting of single covalent bond, NH, N(CH₃), CH₂,CH₃CH, and CH₂CH₂; X^(O) is selected from the group consisting ofhydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl,trifluoromethyl, hydroxymethyl, and fluoro; R¹ is selected from thegroup consisting of hydrido, hydroxy, amino, aminomethyl, methylamino,cyano, methyl, trifluoromethyl, methoxy, methylthio, trifluoromethoxy,fluoro, and chloro; R² is selected from the group consisting of phenyland 2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl,3-isoxazolyl, 2-pyridyl, and 3-pyridyl heteroaryl rings, wherein (a) aring carbon in a first alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R⁹, (b) a ring carbonin a second alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰ (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹² ₁ and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; Y⁰ is selected from the group consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethylthio,methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, carboxy, and cyano. Q^(b) isselected from the group consisting of NR²⁰R²¹ and C(NR²⁵)NR²³R²⁴, withthe proviso that said Q^(b) group is bonded directly to a carbon atom;R²⁰, R²¹, R²³, R²⁴ and R²⁵ are independently selected from the groupconsisting of hydrido, methyl, and ethyl; and Q^(s) is CH₂.
 14. Thecompound as recited in claim 13 or a pharmaceutically acceptable saltthereof, wherein; B is selected from the group consisting of2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl,4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl,3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl,4-methylphenyl, and phenyl; A is selected from the group consisting ofCH₂, CH₃CH, CF₃CH, NHC(O), CH₂CH₂,and CH₂CH₂CH₂; X^(O) is selected fromthe group consisting of hydrido, hydroxy, amino, amidino, aminomethyl,cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro; R¹ isselected from the group consisting of hydrido, hydroxy, amino,aminomethyl, cyano, methyl, trifluoromethyl, and fluoro; R² is selectedfrom the group consisting of 5-amino-3-amidocarbonylphenyl,5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl,3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydrido, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂.
 15. The compound as recited in claim 14 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl,4-methylphenyl, and phenyl; A is selected from the group consisting ofCH₂, NHC(O), CH₂CH₂, and CH₂CH₂CH₂; X^(O) is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano,methyl, trifluoromethyl, hydroxymethyl, and fluoro; R¹ is selected fromthe group consisting of hydrido, hydroxy, amino, aminomethyl, cyano,methyl, trifluoromethyl, and fluoro; R² is selected from the groupconsisting of 3-aminophenyl, benzyl, 3-chlorophenyl,3-dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, phenyl,3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl;and Y⁰ is selected from the group consisting of5-amidino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl,and 3-fluoro4-amdinobenzyl.
 16. A compound as recited in claim 9, or apharmaceutically acceptable salt thereof, wherein: R² is 3-aminophenyl,B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido,and X^(O) is hydrido; R² is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R² is phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, andX^(O) is hydrido; R² is 3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R² is2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ ishydrido, and X^(O) is hydrido; R² is phenyl, B is 3-aminophenyl, A isC(O)NH, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R²is phenyl, B is 3-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ ishydrido, and X^(O) is hydrido; R² is 3-(N-methylamino)phenyl, B isphenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) ishydrido; R² is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂CH₂, Y⁰is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R² is phenyl, Bis 4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, andX^(O) is hydrido; R² is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R² isphenyl, B is phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, andX^(O) is hydrido; R² is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y⁰is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R² is3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,R¹ is hydrido, and X^(O) is hydrido; R² is 3-aminophenyl, B is phenyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydrido; R²is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹is hydroxy, and X^(O) is fluoro; R² is 3-dimethylaminophenyl, B isphenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydroxy, and X^(O) isfluoro; R² is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is phenyl, B is3-aminophenyl, A is C(O)NH, Y⁰ is 4-amidinobenzyl, R¹ is hydroxy, andX^(O) is fluoro; R² is phenyl, B is 3-amidinophenyl, A is CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is3-(N-methylamino)phenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is3-methylsulfonamidophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is phenyl, B is4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydroxy, andX^(O) is fluoro; R² is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰is 4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is phenyl, Bis phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydroxy, and X^(O) isfluoro; R² is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is hydroxy, and X^(O) is fluoro; R² is3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,R¹ is amino, and X^(O) is hydrido; R² is 3-aminophenyl, B is phenyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido; R² isphenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ isamino, and X^(O) is hydrido; R² is 3-dimethylaminophenyl, B is phenyl, Ais CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido; R²is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹is amino, and X^(O) is hydrido; R² is phenyl, B is 3-aminophenyl, A isC(O)NH, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido; R² isphenyl, B is 3-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ isamino, and X^(O) is hydrido; R² is 3-(N-methylamino)phenyl, B is phenyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido;R² is 3-methylsulfonamidophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido; R² is phenyl, B is4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O)is hydrido; R² is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is amino, and X^(O) is hydrido; R² is phenyl, B isphenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ is amino, and X^(O) ishydrido; R² is 3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R1 is amino, and X^(O) is hydrido; R² is 3-aminophenyl,B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B is phenyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido;R² is phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,R¹ is aminomethyl, and X^(O) is hydrido; R² is 3-dimethylaminophenyl, Bis phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, andX^(O) is hydrido; R² is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is phenyl,B is 3-aminophenyl, A is C(O)NH, Y⁰ is 4-amidinobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is phenyl, B is 3-amidinophenyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido;R² is 3-(N-methylamino)phenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is3-methylsulfonamidophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is phenyl,B is 4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-methylaminophenyl, B isphenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O)is hydrido; R² is phenyl, B is phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl,R¹ is aminomethyl, and X^(O) is hydrido; or R² is 3-methylphenyl, B is4-phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, andX^(O) is hydrido.
 17. A compound having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b); A is selected from the group consisting of single covalent bondand (CH(R15))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷); R⁷ isselected from the group consisting of hydrido, hydroxy and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; R¹ and X^(O) are independently selected from the groupconsisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is selectedfrom the group consisting of a covalent single bond, O, S, NH, and CH₂;Q is selected from the group consisting of aryl and heteroaryl wherein(a) a ring carbon in a first alpha position relative to the ring carbonat the point of attachment is optionally substituted by R⁹, (b) a ringcarbon in a second alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R¹³, (c) a ring carbon,in a first beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, andcyano; R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,amidocarbonyl, halo, haloalkyl, and cyano; Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D6, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵ D⁶, J⁵, and J⁶ are N; R¹⁶, R¹⁷,R¹⁸, and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, C(NR²⁵)NR²³R²⁴, andN(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no more than one of R²⁰and R²¹ is hydroxy and that no more than one of R²³ and R²⁴ is hydroxy;R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, alkyl, and hydroxy; and Q^(s) is selectedfrom the group consisting of a single covalent bond, CH₂, and CH₂CH₂.18. The compound as recited in claim 17 or a pharmaceutically acceptablesalt thereof, wherein; B is selected from the group consisting ofhydrido, ethyl, 2-propynyl, 2-propenyl, propyl, isopropyl, butyl,2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl,2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl,2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl,3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl,1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,1-propyl-2-propenyl, 1 -ethyl-2-butynyl, 1 -heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl,4-heptynyl, 5-heptynyl, 2-heptyl, 1 -methyl-2-hexenyl, 1-methyl-3-hexenyl, 1 -methyl-4-hexenyl, 1 -methyl-5-hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1 -ethyl-3-pentenyl, 1 -ethyl4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³ R³⁴, R³⁵, and R³⁶; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b); A is selected from thegroup consisting of single covalent bond, NH, N(CH₃), N(OH), CH₂, CH₃CH,CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂,CH₃CHCH₂, and CF₃CHCH₂; R¹ and X^(O) are independently selected from thegroup consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl,ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,and bromo; R² is Z⁰-Q; Z⁰ is selected from the group consisting of acovalent single O, S, NH, and CH₂; Q is selected from the groupconsisting of phenyl and 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl,3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-ylheteroaryl rings, wherein (a a ring carbon in a first alpha positionrelative to the ring carbon at the point of attachment is optionallysubstituted by R⁹, (b) a ring carbon in a second alpha position relativeto the ring carbon at the point of attachment is optionally substitutedby R¹³, (c) a ring carbon, in a first beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R⁹, is optionally substituted byR¹⁰, (d) a ring carbon, in a second beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹³, is optionally substitutedby R¹², and (e) a ring carbon, if present, in the gamma positionrelative to the ring carbon at the point of attachment and in an alphaposition relative to each of the ring atoms optionally substituted byR¹⁰ and R¹², respectively, is optionally substituted by R¹¹; R⁹, R¹¹,and R¹³ are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:

R¹⁶ , R¹⁷ , R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,C(N R²⁵ )N R²³R²⁴ , and N (R ²⁶)C(N R²⁵ )N(R ²³ )(R ²⁴), with theprovisos that no more than one of R²⁰ and R ²¹ is hydroxy at the sametime and that no more than one of R²³ and R²⁴ is hydroxy; R²⁰, R²¹, R²³,R²⁴, R²⁵, and R²⁶ are independently selected from the group consistingof hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy; andQ^(s) is selected from the group consisting of a single covalent bond,CH₂, and CH₂CH₂.
 19. The compound as recited in claim 18 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl,isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl, tert-butyl,isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl,2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl,3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl,3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl,and 4-aminobutyl; A is selected from the group consisting of singlecovalent bond, CH₂, NHC(O), CH₂CH₂, CH₂CH₂CH₂, and CH₃CHCH₂; R¹ andX^(O) are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano,methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino,methylthio, trifluoromethoxy, fluoro, and chloro; R² is Z⁰-Q; Z⁰ isselected from the group consisting of a covalent single O, S, NH, andCH₂; Q is selected from the group consisting of5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydrido, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(N R²⁵)N R²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂.
 20. The compound as recited in claim 17 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of hydrido C2-C8 alkyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b); A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);R⁷ is selected from the group consisting of hydrido and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; R¹ and X^(O) are independently selected from the groupconsisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is acovalent single bond; Q is selected from the group consisting of aryland heteroaryl wherein (a) a ring carbon in a first alpha positionrelative to the ring carbon at the point of attachment is optionallysubstituted by R⁹, (b) a ring carbon in a second alpha position relativeto the ring carbon at the point of attachment is optionally substitutedby R¹³, (c) a ring carbon, in a first beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R⁹, is optionally substituted byR¹⁰, (d) a ring carbon, in a second beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹³, is optionally substitutedby R¹², and (e) a ring carbon, if present, in the gamma positionrelative to the ring carbon at the point of attachment and in an alphaposition relative to each of the ring atoms optionally substituted byR¹⁰ and R¹², respectively, is optionally substituted by R¹¹; R⁹, R¹¹,and R¹³ are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ isformula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D5,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵ D⁶, J⁵, and J6 are N; R¹⁶, R¹⁷,R¹⁸, and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), andC(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴ ₁ R²⁵, and R²⁶ are independentlyselected from the group consisting of hydrido and alkyl; and Q^(s) isCH₂.
 21. The compound as recited in claim 17 or a pharmaceuticallyacceptable salt thereof, wherein; B is selected from the groupconsisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl,3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and3,3,3-trifluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including 5 atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guanidino,methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, andQ^(b); A is selected from the group consisting of: (i) a single covalentbond, NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂; and (ii) CH₂N(CH₃),CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido; X^(O) is selected from the group consisting of hydrido,hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,hydroxymethyl, and fluoro; R¹ is selected from the group consisting ofhydrido, hydroxy, amino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, methylthio, trifluoromethoxy, fluoro, andchloro; R² is selected from the group consisting of phenyl and2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,2-pyridyl, and 3-pyridyl heteroaryl rings, wherein (a) a ring carbon ina first alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R⁹, (b) a ring carbon in asecond alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; Y⁰ is selected from the group consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethylthio,methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, carboxy, and cyano. Q^(b) isselected from the group consisting of NR²⁰R²¹, C(NR²⁵)NR²³R²⁴, andN(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that said Q^(b) group isbonded directly to a carbon atom; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ areindependently selected from the group consisting of hydrido, methyl, andethyl; and Q^(s) is CH₂.
 22. The compound as recited in claim 21 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl,isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl, tert-butyl,isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl,2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl,3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl,3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl,and 4-aminobutyl; A is selected from the group consisting of singlecovalent bond, CH₂, CH₃CH, and CH₂CH₂; X^(O) is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano,methyl, trifluoromethyl, hydroxymethyl, and fluoro; R¹ is selected fromthe group consisting of hydrido, hydroxy, amino, aminomethyl, cyano,methyl, trifluoromethyl, and fluoro; R² is selected from the groupconsisting of 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydrido, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂. 23-24. (canceled)
 25. A compound having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of C3-C7 cycloalkyl and C4 saturatedheterocyclyl, wherein (a) each ring carbon is optionally substitutedwith R³³, (b) a ring carbon, other than the ring carbon at the point ofattachment, is optionally substituted with oxo provided that no morethan one ring carbon is substituted by oxo at the same time, (c) a ringcarbon or nitrogen in a first alpha position relative to the ring carbonat the point of attachment is optionally substituted by R⁹, (d) a ringcarbon or nitrogen in a second alpha position relative to the ringcarbon at the point of attachment is optionally substituted by R¹³, (e)a ring carbon or nitrogen, if present, in a first beta position relativeto the ring carbon at the point of attachment and in an alpha positionrelative to the ring atom optionally substituted by R⁹, is optionallysubstituted by R¹⁰, (f) a ring carbon or nitrogen, if present, in asecond beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², (g) a ring carbonor nitrogen, if present, in a first gamma position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹⁰, is optionally substitutedby R¹¹, and (h) a ring carbon or nitrogen, if present, in a second gammaposition relative to the carbon at the point of attachment and in analpha position relative to the ring atom optionally substituted by R¹²,is optionally substituted by R³³: R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, andcyano; R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,amidocarbonyl, halo, haloalkyl, and cyano; R³³ and R³⁴ are independentlyselected from the group consisting of hydrido, acetamido, haloacetamido,amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, loweralkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is selected fromthe group consisting of single covalent bond and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷); R⁷ isselected from the group consisting of hydrido, hydroxy and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; R¹ and X^(O) are independently selected from the groupconsisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is selectedfrom the group consisting of a covalent single O, S, NH, and CH₂; Q isselected from the group consisting of aryl and heteroaryl wherein (a) aring carbon in a first alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R⁹, (b) a ring carbonin a second alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, and C(NR²⁵)NR²³R²⁴, with the provisosthat no more than one of R²⁰ and R²¹ is hydroxy and that no more thanone of R²³ and R²⁴ is hydroxy; R²⁰, R²¹, R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido, alkyl, andhydroxy; and Q^(s) is selected from the group consisting of a singlecovalent bond, CH₂, and CH₂CH₂.
 26. The compound as recited in claim 25or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of cyclopropyl, cyclobutyl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl,cyclohexyl, norbornyl, bicyclo[3.1.0]hexan-6-yl, and cycloheptyl,wherein (a) each ring carbon is optionally substituted with R³³, (b) aring carbon or nitrogen in a first alpha position relative to the ringcarbon at the point of attachment is optionally substituted by R⁹, (c) aring carbon or nitrogen in a second alpha position relative to the ringcarbon at the point of attachment is optionally substituted by R¹³, (d)a ring carbon or nitrogen, if present, in a first beta position relativeto the ring carbon at the point of attachment and in an alpha positionrelative to the ring atom optionally substituted by R⁹, is optionallysubstituted by R¹⁰, and (e) a ring carbon or nitrogen, if present, in asecond beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹²; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; R³³ and R34 are independently selected fromthe group consisting of hydrido, amidino, guanidino, carboxy, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b); A is selected from the group consisting of single covalentbond, NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂; R¹ and X^(O) areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰-Q; Z⁰ isselected from the group consisting of a covalent single O, S, NH, andCH₂; Q is selected from the group consisting of phenyl and 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl heteroaryl rings, wherein (a) aring carbon in a first alpha position relative to the ring carbon at thepoint of attachment is optionally substituted by R⁹, (b) a ring carbonin a second alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; Y⁰ is selected from the group consistingof:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; Q^(b) is selected from the group consisting of hydrido andC(NR²⁵)NR²³R²⁴, with the proviso that no more than one of R²³ and R²⁴ ishydroxy at the same time; R²³, R²⁴, and R²⁵ are independently selectedfrom the group consisting of hydrido, methyl, ethyl, and hydroxy; andQ^(s) is selected from the group consisting of a single covalent bond,CH₂ and CH₂CH₂.
 27. The compound as recited in claim 26 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,andbicyclo[3.1.0]hexan-6-yl; A is selected from the group consisting ofsingle covalent bond, CH₂, NHC(O), CH₂CH₂, and CH₂CH₂CH₂; R¹ and X^(O)are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano,methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino,methylthio, trifluoromethoxy, fluoro, and chloro; R² is Z⁰-Q; Z⁰ isselected from the group consisting of a covalent single O, S, NH, andCH₂; Q is selected from the group consisting of5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydride, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂.
 28. The compound as recited in claim 25 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of C3-C7 cycloalkyl and C4 saturatedheterocyclyl, wherein (a) each ring carbon is optionally substitutedwith R³³, (b) a ring carbon, other than the ring carbon at the point ofattachment, is optionally substituted with oxo provided that no morethan one ring carbon is substituted by oxo at the same time, (c) a ringcarbon or nitrogen in a first alpha position relative to the ring carbonat the point of attachment is optionally substituted by R⁹, (d) a ringcarbon or nitrogen in a second alpha position relative to the ringcarbon at the point of attachment is optionally substituted by R¹³, (e)a ring carbon or nitrogen, if present, in a first beta position relativeto the ring carbon at the point of attachment and in an alpha positionrelative to the ring atom optionally substituted by R⁹, is optionallysubstituted by R¹⁰, (f) a ring carbon or nitrogen, if present, in asecond beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², (g) a ring carbonor nitrogen, if present in a first gamma position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹⁰, is optionally substitutedby R¹¹ ₁ and (h) a ring carbon or nitrogen, if present, in a secondgamma position relative to the carbon at the point of attachment and inan alpha position relative to the ring atom optionally substituted byR¹², is optionally substituted by R³³; R⁹, R¹¹, and R¹³ areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyalkyl, carboxyamido, and cyano; R³³ and R³⁴are independently selected from the group consisting of hydrido,amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, loweralkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, and cyano; A is selected from thegroup consisting of single covalent bond and (CH(R¹⁵))_(pa)—(W⁷)_(rr)wherein rr is an integer selected from 0 through 1, pa is an integerselected from 0 through 3, and W⁷ is N(R⁷); R⁷ is selected from thegroup consisting of hydrido and alkyl; R¹⁵ is selected from the groupconsisting of hydrido, halo, alkyl, and haloalkyl; R¹ and X^(O) areindependently selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo; R² is Z⁰-Q; Z⁰ is a covalent single bond; Q is selected fromthe group consisting of aryl and heteroaryl wherein (a) a ring carbon ina first alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R⁹, (b) a ring carbon in asecond alpha position relative to the ring carbon at the point ofattachment is optionally substituted by R¹³, (c) a ring carbon, in afirst beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R⁹, is optionally substituted by R¹⁰, (d) a ring carbon,in a second beta position relative to the ring carbon at the point ofattachment and in an alpha position relative to the ring atom optionallysubstituted by R¹³, is optionally substituted by R¹², and (e) a ringcarbon, if present, in the gamma position relative to the ring carbon atthe point of attachment and in an alpha position relative to each of thering atoms optionally substituted by R¹⁰ and R¹², respectively, isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkoxy, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;R¹⁰ and R¹² are independently selected from the group consisting ofhydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino,alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy,carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, and C(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴,and R²⁵ are independently selected from the group consisting of hydridoand alkyl; and Q^(s) is CH₂.
 29. The compound as recited in claim 28 ora pharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, andbicyclo[3.1.0]hexan-6-yl, wherein (a) each ring carbon is optionallysubstituted with R³³, (b) a ring carbon or nitrogen in a first alphaposition relative to the ring carbon at the point of attachment isoptionally substituted by R⁹, (c) a ring carbon or nitrogen in a secondalpha position relative to the ring carbon at the point of attachment isoptionally substituted by R¹³, (d) a ring carbon or nitrogen, ifpresent, in a first beta position relative to the ring carbon at thepoint of attachment and in an alpha position relative to the ring atomoptionally substituted by R⁹, is optionally substituted by R¹⁰, and (e)a ring carbon or nitrogen, if present, in a second beta positionrelative to the ring carbon at the point of attachment and in an alphaposition relative to the ring atom optionally substituted by R¹³, isoptionally substituted by R¹²; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; R³³ is selected from the group consisting of hydrido, amidino,guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino,N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl,cyano, and Q^(b); A is selected from the group consisting of singlecovalent bond, NH, N(CH₃), CH₂, CH₃CH, CH₂CH₂, and CH₂CH₂CH₂; X^(O) isselected from the group consisting of hydrido, hydroxy, amino, amidino,aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;R¹ is selected from the group consisting of hydrido, hydroxy, amino,aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,methylthio, trifluoromethoxy, fluoro, and chloro; R² is selected fromthe group consisting of phenyl and 2-thienyl, 2-furyl, 2-pyrrolyl,2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridylheteroaryl rings, wherein (a) a ring carbon in a first alpha positionrelative to the ring carbon at the point of attachment is optionallysubstituted by R⁹, (b) a ring carbon in a second alpha position relativeto the ring carbon at the point of attachment is optionally substitutedby R¹³, (c) a ring carbon, in a first beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R⁹, is optionally substituted byR¹⁰, (d) a ring carbon, in a second beta position relative to the ringcarbon at the point of attachment and in an alpha position relative tothe ring atom optionally substituted by R¹³, is optionally substitutedby R¹², and (e) a ring carbon, if present, in the gamma positionrelative to the ring carbon at the point of attachment and in an alphaposition relative to each of the ring atoms optionally substituted byR¹⁰ and R¹², respectively, is optionally substituted by R¹¹; Y⁰ isselected from the group consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethylthio,methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, carboxy, and cyano. Q^(b) isselected from the group consisting of NR²⁰R²¹ and C(NR²⁵)NR²³R²⁴, withthe proviso that said Q^(b) group is bonded directly to a carbon atom;R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, methyl, and ethyl; and Q^(s) is CH₂.
 30. Thecompound as recited in claim 29 or a pharmaceutically acceptable saltthereof, wherein; B is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,azetidin-2-yl,and azetidin-3-yl; A is selected from the group consistingof a single covalent bond, CH₂, NHC(O), CH₂CH₂ and CH₂CH₂CH₂; X^(O) isselected from the group consisting of hydrido, hydroxy, amino, amidino,aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;R¹ is selected from the group consisting of hydrido, hydroxy, amino,aminomethyl, cyano, methyl, trifluoromethyl, and fluoro; R² is selectedfrom the group consisting of 3-aminophenyl, 2,6-dichlorophenyl,2-hydroxyphenyl, 5-amino-2-thienyl, and 3-thienyl; Y⁰ is selected fromthe group consisting of:

R¹⁶ and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy,hydroxymethyl, fluoro, chloro, and cyano; R¹⁷ and R¹⁸ are independentlyselected from the group consisting of hydrido, fluoro, chloro, hydroxy,hydroxymethyl, amino, carboxy, and cyano; Q^(b) is selected from thegroup consisting of hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido and methyl;and Q^(s) is CH₂.
 31. The compound as recited in claim 30 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,azetidin-2-yl,and azetidin-3-yl; A is selected from the group consistingof a single covalent bond, CH₂, CH₂CH₂ and CH₂CH₂CH₂; X^(O) is selectedfrom the group consisting of hydrido, hydroxy, amino, amidino,aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;R¹ is selected from the group consisting of hydrido, hydroxy, amino,aminomethyl, cyano, methyl, trifluoromethyl, and fluoro; R² is selectedfrom the group consisting of 3-aminophenyl, 2,6-dichlorophenyl,2-hydroxyphenyl, phenyl, 5-amino-2-thienyl, and 3-thienyl; and Y⁰ isselected from the group consisting of 5-amidino-2-thienylmethyl,4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amdinobenzyl.32. A compound as recited in claim 25, or a pharmaceutically acceptablesalt thereof, wherein: R² is 3-aminophenyl, B is cycylopropyl, A issingle bond, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O) ishydrido; R² is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is aminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B iscyclopropyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B is cyclobutyl,A is single bond, Y⁰ is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O) ishydrido; R² is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is5-amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is aminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B is cyclohexyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R1 is aminomethyl, and X^(O) ishydrido; R² is 2-hydroxyphenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is phenyl,B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, R¹ isaminomethyl, and X^(O) is hydrido; R² is 3-thienyl, B is cyclobutyl, Ais single bond, Y⁰ is 4-amidinobenzyl, R1 is aminomethyl, and X^(O) ishydrido; R² is 2,6-dichlorophenyl, B is cyclobutyl, A is single bond, Y⁰is 4-amidinobenzyl, R¹ is aminomethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cycylopropyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R²is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R² is3-aminophenyl, B is cyclopropyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R²is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R²is 3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R² is5-amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl; R² is3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ ishydrido, and X^(O) is hydroxymethyl; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is hydrido, and X^(O) is hydroxymethyl; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, R¹ ishydrido, and X^(O) is hydroxymethyl; R² is 3-aminophenyl, B iscyclohexyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O)is hydroxymethyl; R² is 2-hydroxyphenyl, B is cyclobutyl, A is singlebond, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) is hydroxymethyl;R² is phenyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is hydrido, and X^(O) is hydroxymethyl; R² is 3-thienyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, andX^(O) is hydroxymethyl; R² is 2,6-dichlorophenyl, B is cyclobutyl, A issingle bond, Y⁰ is 4-amidinobenzyl, R¹ is hydrido, and X^(O) ishydroxymethyl; R² is 3-aminophenyl, B is cycylopropyl, A is single bond,Y⁰ is 4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R²is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclopropyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R²is 3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R²is 3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R² is5-amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido; R² is3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰ is 4-amidinobenzyl, R¹ ishydroxymethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is hydroxymethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, R¹ ishydroxymethyl, and X^(O) is hydrido; R² is 3-aminophenyl, B iscyclohexyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, R¹ is hydroxymethyl, andX^(O) is hydrido; R² is 2-hydroxyphenyl, B is cyclobutyl, A is singlebond, Y⁰ is 4-amidinobenzyl, R¹ is hydroxymethyl, and X^(O) is hydrido;R² is phenyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl,R¹ is hydroxymethyl, and X^(O) is hydrido; R² is 3-thienyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, R¹ ishydroxymethyl, and X^(O) is hydrido; or R² is 2,6-dichlorophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, R¹ ishydroxymethyl, and X^(O) is hydrido. 33-46. (canceled)
 47. A compositionfor inhibiting thrombotic conditions in blood comprising a compound ofany one of claims 9, 17, and 25 and a pharmaceutically acceptablecarrier.
 48. A method for inhibiting thrombotic conditions in bloodcomprising adding to blood a therapeutically effective amount of acomposition of and claim
 47. 49. A method for inhibiting formation ofblood platelet aggregates in blood comprising adding to blood atherapeutically effective amount of a composition of claim
 47. 50. Amethod for inhibiting thrombus formation in blood comprising adding toblood a therapeutically effective amount of a composition of claim 47.51. A method for treating or preventing venuous thromboembolism andpulmonary embolism in a mammal comprising administering to the mammal atherapeutically effective amount of a composition of claim
 47. 52. Amethod for treating or preventing deep vein thrombosis in a mammalcomprising administering to the mammal a therapeutically effectiveamount of a composition of claim
 47. 53. A method for treating orpreventing cardiogenic thromboembolism in a mammal comprisingadministering to the mammal a therapeutically effective amount of acomposition of claim
 47. 54. A method for treating or preventingthromboembolic stroke in humans and other mammals comprisingadministering to the mammal a therapeutically effective amount of acomposition of claim
 47. 55. A method for treating or preventingthrombosis associated with cancer and cancer chemotherapy in humans andother mammals comprising administering to the mammal a therapeuticallyeffective amount of a composition of claim
 47. 56. A method for treatingor preventing unstable angina in humans and other mammals comprisingadministering to the mammal a therapeutically effective amount of acomposition of claim
 47. 57. A method for inhibiting thrombus formationin blood comprising adding to blood a therapeutically effective amountof a compound of any one of claims 9, 17, and 25 with a therapeuticallyeffective amount of fibrinogen receptor antagonist.
 58. (canceled)